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245 Cards in this Set
- Front
- Back
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Test sensitivity
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No false negatives
the ability of a test to identify disease in diseased animals If diseased, must be positive |
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Test specificity
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No false positives
the ability of a test to identify health in healthy animals If no disease, must be negative |
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Positive predictive value
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The probability of an animal with a positive test result actually has the disease
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Negative predictive value
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The probability of an animal with a negative test result actually does not have the disease
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Influences of predictive value
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Disease prevelance has strong affect on predictive value: higher prevelance, greater predictive value
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Significance of Test bias
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=Accuracy/systemic error
how close the test result is to the true value |
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Significance of Precision
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=CV/ Random error
How reproducible the test results are |
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Requirements of a "good test"
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Test Bias
Precision |
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Primary Urinary profiles
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BUN
Creatinine UA -physical, chemical, sediment |
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Secondary Urinary profiles
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Electrolytes
Acid-Base profile |
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Primary Liver profile for LA
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AST
SDH GGT ALP Bilirubin |
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Secondary Liver profile for LA
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Glucose
BUN Cholesterol Protein |
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Primary Liver profile for SA
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ALT
AST ALP GGT Bilirubin |
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Secondary Liver profile for SA
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Glucose
BUN Protein Cholesterol |
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Fluid/electrolytes profile
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Serum Profile
Hematocrit BUN, Creatinine, Urine S.G. Electrolytes Acid-base profile |
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Muscle Profile
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CK
AST Potassium Myoglobinemia/uria |
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Primary Pancreas/Carb profile
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Glucose
UA-glucose, ketones |
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Secondary Pancreas/Carb profile
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Acid-base profile
liver profile electrolytes amylase/lipase |
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Gastrointestinal profiles
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Serum proteins
Electrolytes Acid-base electrolytes |
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Two types of marrow
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Red=hematopoietic
Yellow=adipose |
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Sites of marrow hematopoietic activity
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all bones in young animals
flat bones & epiphysis of long bones in older animals |
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Multipotential stem cells
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look like small lymphocytes
divide & replace themselves & to produce differentiated/ committed progenitor cells |
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Growth factors influencing hematopoiesis
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IL-3, Granulocyte-macrophage colony stim. factor (GM-CSF),
Granulocyte-CSF Stem Cell Factor Erythropoietin Thrombopoietin |
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Effect of IL-3 on hematopoiesis
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it's a multipotential CSF
made by T lymphs -supports growth of stem cells & committed precursors |
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Effect of Granulocyte-Macrophage colony stimulating factor (GM-CSF)
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made by T cells, endothelial cells & fibroblasts
-supports growth of CFU-GM, BFU-E & CFU-Meg |
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Effect of Stem Cell Factor
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Made by Stromal cells in bone marrow
-stimulate other cells to enter the cell cycle -work with other cytokines, to increase size & number of colonies |
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Effect of Granulocyte-colony stimulating factor (G-CSF)
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made by T cells, endothelial cells & fibroblasts
-supports the terminal differentiation of neutrophils |
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Effect of Erythropoietin
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Made in kidney
-supports BFU-E, CFU-E and the terminal differentiation of erythroid cells |
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Effect of Thrombopoietin
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Made in liver & kidney
-regulated by mature platelets -stimulate BFU-MK to proliferate & differentiate -cause megakaryocytes to enlarge, endoreduplication & release proplatelets |
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Normal erythropoiesis
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balanced replacement of RBCs lost in health (1%/day)
4 divisions=16 RBCs (rubricytes) takes 5 days from stem cells to retic release |
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Stages of RBC maturation
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Rubiblast
Prorubricytes Rubricyte Metarubricyte Retic Erythrocyte Hemoglobin concentrations increases from early Rub. to late Rub.= shuts off division |
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Metarubricytes
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Small, pyknotic nucleus-ready to extrude
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Reticulocytes
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Nucleus already extruded, but still contains RNA & organelles
Released in marrow sinus (-EQ) Take another 24 hours to mature |
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Staining Retics
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Wrights stain=polychromatophil
NMB=retic |
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Rubriblast
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1st morphologically identified erythroid cell
big, round nucleus single nucleolus |
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Characteristics of mature erythrocyte
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No DNA/RNA
Fully hemoglobinized |
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Average RBC lifespan
-in dog -in cat -in horse -in cow |
dog-110
cat-70 horse-145 cow-150 |
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Control of heme synthesis
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Aminolevulinic acid synthetase
Porphyrins |
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Aminolevulinic acid synthetase
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The rate limiting step of Heme synthesis
under negative feedback control from [heme] in RBC Sensitive to Lead toxicosis |
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Significance of Porphyrins
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Intermediates of heme biosynthesis
deficiencies of the enzymes in this pathway can cause disease |
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Functions of RBCs
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Oxygen delivery to tissues
CO2 transport H+ buffering Maintain vascular integrity -NO, ADPase, adenine nucleotides Coagulation |
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Important pathways in erythrocyte metabolism
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Embden-Meyerhof pathway
Hexose-monophosphate pathway Methemoglobin reductase Leubering-Rapoport pathway |
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Significance of Embden-Meyerhof Pathway
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generates ATP & NADH
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Significance of Hexose-monophosphate pathway
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Prevents oxidative injury to RBCs
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Significance of Methomoglobin reductase pathway
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Keeps hemoglobin in reduced (Fe2+) form
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Significance of Luebering-Rapoport Pathway
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forms 2,3 DPG
-causes a right shift in oxygen dissociation curve |
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Mechanism of Extravascular hemolysis
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Primary mechanism for removal of RBCs from circulation
RBCs are phagocytized by macrophages |
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Macrophage processing of Hemoglobin molecule
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Hemoglobin is broken down to Heme & Globin
Globin→amino acids→reutilized Heme→unconj. bilirub + albumin→ liver→ conjug. bilirub→ bile→ intestines |
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Mechanisms of intravascular hemolysis
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a minor route of removing RBCs
RBCs lyse in ciculation, spilling Hb Hb & haptoglobin→picked up and processed by hepatic macrophages |
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Overload of the Haptoglobin recovery system
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Hb oxidized to MetHb (Fe3+)→free heme (Fe3+)→ complexed by hemopexin→liver→bile
prevents renal damage by heme |
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Purpose of Haptoglobin
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to bind free hB in circulation, preventing it from being lost (via urine)
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Definition of Hematology
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Study of the nature & disease of blood & blood forming organs
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Definition of Clinical Hematology
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Utilize information derived from the study of blood, to diagnose & treat disease
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Constituents of Serum
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Red Top
centrifuged liquid portion of blood after it clots |
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Constituents of Plasma
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Green (blue, purple) top
centrifuged liquid portion of blood with anticoagulant (no clotting) Contains Fibrinogen & Coagulation proteins |
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Plasma Proteins
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Albumin
Globulins -immunoglobulin -transport proteins -acute phase proteins -coagulation proteins |
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Plasma electrolyte cations
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Sodium
Potassium Calcium Magnesium |
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Plasma electrolyte anions
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Chloride
Bicarb Phosphate Sulfate |
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Mechanisms of anticoagulants
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EDTA-Chelates calcium
Heparin-Activates antithrombin III Citrate Oxalate |
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Compensatory mechanisms for anemia
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↓O2 affinity for Hb
-2,3 DPG-shift dissociation curve to the right vasodilation-↑tissue perfusion ↑CO ↑Respiratory rate ↑RBC production -via erythropoietin |
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What mechanisms cause Hct, Hb, and RBC numbers to ↑?
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Polycythemia
-primary-increased production -relative (dehydration) |
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What mechanisms cause Hct, Hb, and RBC numbers to ↓?
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Anemia
Overhydration |
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Determining severity of anemia
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Must consider hydration status
-do before giving fluids -use PP to assess |
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Assessing anemia in dogs using PCV
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30-37%=mild
20-29%=moderate 13-19%=severe |
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Assessing anemia in cats using PCV
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20-26%=mild
14-19=moderate 10-13=severe |
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Causes of Macrocytic, Hypochromic anemias
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REGENERATIVE
-hemolytic -blood loss |
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Causes of Normocytic, Normochromic anemias
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NON-REGENERATIVE
-Reduced erythropoiesis -Ineffective/Defective erythropoiesis |
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Characteristics of Hemolytic anemias
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REGENERATIVE
Macrocytic, Hypochromic IMHA Oxidative injury Metabolic Parasitic Drug-induced |
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Characteristics of Blood loss anemias
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REGENERATIVE
Macrocytic, Hypochromic Internal and/or external losses |
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Characteristics of Reduced erythropoiesis anemias
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NON-REGENERATIVE
Anemia of chronic Dz Lack of erythropoietin FeLV Iron deficiency Red cell aplasia |
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Characteristics of infective/defective erythropoiesis
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NON-REGENERATIVE
normocytic, normochromic Aplastic anemia Myelophthisic anemia |
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Microcytosis
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RBCs smaller than normal
due to decreased Hb synthesis allows extra division of rubricytes |
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Factors causing ↓ in MCV
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Iron deficiency
Portosystemic shunts Akita/Asian breeds |
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What is MCH?
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Mean corpuscular hemoglobin
average concentration of hemoglobin in a RBC in picograms (not used as much as MCHC-more accurate) |
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Factors causing ↓ in MCHC
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RETICULOCYTOSIS
Iron deficiency |
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Factors causing false ↑ in MCHC
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in vitro/vivo hemolysis
-lipemia -hienz bodies -oxyhemoglobin -marked leukocytosis -marked hyperproteinemia |
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Canine Reticulocytes
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~1% normally in health
mature to in about 24 hours Count all seen |
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Feline Reticulocytes
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~0.4% normally in health
two types of retics -aggregates- count these 12-24 hours to mature -punctate- don't count 10-14 DAYS to mature |
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Reticulocyte Production Index
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Exaggerates the retic %
Accounts for immature retics staying in circulation longer than normal Corr. retic x 1/matur. time |
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Maturation times based on PCVs
a.45% b.35% c.25% d.15% |
a 1.0
b 1.5 c 2.0 d 2.5 |
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Absolute retic count
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Best indicator of bone marrow production
but requires RBC count =Retic % x RBC count |
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Effect of Reticulocytosis on CBC parameters
MCH MCHC MCV |
MCH~normal
MCHC-decreased MCV-increased |
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Ability of different species to respond to anemias
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Dog-greatest ability
cat cow horse-least ability |
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Significance of nRBCs in circulation
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Should be associated with reticulocytosis
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Abnormal causes of nRBCs in circulation
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Splenectomy
Bone marrow stromal damage extramedullary hematopoiesis lead toxicity bone fracture leukemia corticosteroids Change to microenvironment of hematopoietic organs |
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What is anisocytosis?
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Variation in RBC Size
normal in cats & cows |
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Slide indications of Regenerative anemia
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Polychromasia
Anisocytosis +/-nRBC +/-Howell-Jolly bodies +/-basophilic stippling |
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Indications of Regeneration from CBC data
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↓MCHC
↑MCV ↑RDW ↑Retic count/% ↑#nRBCs |
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What are the 3 Major classes of Anemic causes?
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Loss of RBC-hemorrhage
Destroy RBC-hemolysis Don't make RBC-production failure |
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Characteristics of acute hemorrhage
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Cells, plasma & protein all lost in equal portions
Hct remains the same initially |
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Effect of Epinephrine release
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Causes splenic contraction
-massive release of RBC, WBC & platelets Hct up to 80% |
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Initial response to acute hemorrhage & CBC changes
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Fluids move from interstial tissue to intervascular space
dilutes cells & proteins= anemia & hypoproteinemia Retic/polychromasia=2-3 days |
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Reticulocytosis after acute blood loss
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response take 2-3 days to develop
maximum response in 5-7 days resolves in 1-2 weeks |
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Characteristics of Chronic hemorrhage
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Slowly developing anemia allows to adapt to ↓ oxygen
Increased erythropoiesis & 2,3 DPG allow Hct to get very low before clinical signs seen leads to depletion of iron |
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Characteristics of Iron Deficiency Anemia
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Decreased Hb production
-Rubricytes take longer to reach critical levels, undergo extra division=small RBCs & ↑ central pallor =microcytic, hypochromic Non/poorly responsive |
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Constellation of Data for
Chronic Hemorrhage |
Anemia
-increasingly microcytic -hypochromic -less regenerative -schistocytes Panhypoproteinemia (A:G=1:1) Thrombocytosis |
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Characteristics of Extravascular hemolysis
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↑ RBCs phagocytosis by macrophages in spleen/liver
-usually marked w/antibody or RBC parasite |
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Typical CBC data of Hemolytic anemia
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+ Coombs test (direct agglutination)
Autoagglutination Spherocytes Leptocytes Hyperbilirubinemia +++Reticulocytosis |
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What are Leptocytes? & what do they signify?
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Target cells
common in responding (hemolytic) anemias due altered membrane:lipid with skipped division during maturation |
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Macrophage digestion of hemoglobin
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scavenge Fe to allow for more immediate reutilization
Heme is converted to bilirubin to be processed by the liver |
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Why does a bruise have its distinct colors?
a. Red-brown b. Green c. Yellow |
a. Heme ring
-hemoxygenase breaksdown to b. bilivirdin & CO -Bilivirdin reductase to c. unconjugated bilirubin |
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Constellation of Extravascular hemolysis
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Chronic insidious onset
Regenerative response Increased (or normal) PP +/- hyperbilirubinemia |
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Key distinguishing feature of intravascular hemolysis?
what to look for to know? |
Hemoglobinemia
+/- hemoglobinuria Hyperbilirubinemia- days later Bilirubinemia Hyperchromic-↑MCHC, Hb |
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Significance of Hemoglobin recovery system
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Fe toxic to kidney b/c causes redox rxn in tubules
Need to conserve Fe, b/c only limited supply |
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Signs of hemoglobinemia
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hemoglobinuria
brownish-red serum |
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Unconjugated Bilirubin
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insoluble in water
what is initially released, with RBC lysis Measured as indirect bilirubin |
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Conjugated Bilirubin
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water soluble
what is released after being processed by the liver Measured as direct bilirubin |
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Causes to Heinz body formation
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Onions, garlic
Acetominophen Red maple toxicosis Copper, zinc Diabetes mellitus hyperthyroidism 10% normal in cats Phenothiazine |
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Significance of the presence of Heinz bodies
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Irreversible injury
-hemoglobin doesn't function -causes membrane abnormality weakened-lyse in circulation (seen as ghost cells) |
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Ghost Cells
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Lysed RBCs with Heinz bodies weakening the membrane
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How are Heinz bodies formed?
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Chemicals that seek electrons
steal them from Hb cause S-S bonds to form in Hb -denatures the Hb, precipitates out & no longer functions in carrying O2 |
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Heinz bodies in cats
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~10% normal
more susceptible to oxidative injury b/c have 8 SH groups (other only have 2) lower methemoglobin reductase & less efficient spleen for removing from circulation |
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Fragmentation anemia
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Intravascular strands of fibrin/altered vessels
-cleave RBCs =schistocytes |
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What are schistocytes?
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Fragments of RBCs
Irregular shapes Seen w/ fragmentation anemias & iron deficiency anemias |
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Significance of Pyruvate Kinase Deficiency?
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Impaired energy metabolism
causing premature RBC destruction ↑ 2,3 DPG-blood O2 saturation increases to compensate -usually exercise intolerant |
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Signs of a pyruvate kinase deficiency
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Moderate-severe anemia
Macrocytic, hypochromic Marked reticulocytosis No RBC morph changes |
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Signs of Phosphofructokinase deficiency
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Persistent compensated anemia
PCV normal/slightly decreased Moderate reticulocytosis RBCs highly fragile |
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Parasitic causes of hemolytic anemia
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Anaplasma
Babesiosis Haemobartonella Eperythrozoonosis Sarcocytosis Trypanosoma Theileriosis Cytauxzoonosis (cats) |
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Bacterial causes of hemolytic anemia
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Lepto
-bacillary hemoglobinuria |
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Viral causes of hemolytic anemia
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Equine Infectious Anemia
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Mechanism of Anemia of Chronic disease
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A production failure b/c iron is diverted to macrophages & hepatocytes, makes less available for hematopoiesis
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Theory behind Anemia of Chronic Disease
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A protective measure makes less iron available to bacteria
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Characteristics of anemia of chronic disease
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Moderate anemia (Hct~20%)
Normocytic, Normochromic Anemia resolves when overlying condition resolved Nonresponsive to iron injections |
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Anemia of chronic renal disease
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Production failure
occurs when many nephrons are lost, erythropoeitin producing cells |
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Granulopoiesis
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production of:
neutrophils Eos Basophils (usually refer to neutrophils) |
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Bone marrow stromal cells
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Fibroblasts
adipose Macrophages Monocytes Lymphs |
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Products of Bone marrow stromal cells
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Extracellular matrix proteins
Cytokines inhibitory factors adhesion molecules |
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Regulation of granulopoiesis by T-lymphocytes & macrophages
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Growth factors
Colony stimulating factors Lymphokines Cytokines |
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Action of Colony stimulating factors
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Increase/promote cellular function
stim. bone marrow release of neutrophils promote neutrophil diapedeis induce chemotaxis enhance phagocytosis & microbicidal activity |
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Population of proliferating pool of neutrophils in bone marrow
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Myeloblast
Promyelocyte Myelocyte (3 stages) 4-5 divisions |
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Population of nonproliferating pool of neutrophils in bone marrow
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=Maturation & Storage pools
Metamyelocytes Band Seg No further division ~5 days supply in health |
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Peculiarities of cow nonproliferating pool
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they don't have a storage pool, do have a maturation pool
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Advantages of Automated counters
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Saves time
More reproducible (less error) |
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Disadvantages of Automated counters (in general)
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Need trained operators
-Requires proper handling & analysis -recognize abnormal findings & instrument malfunction -conduct maintenance/troubleshoot |
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Limits of Impedance automated counters (WIC)
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all nucleated cells counted as WBC
some platelets counted as RBCs Platelet clumps counted as WBC Leukocyte clumps undercounted RBCs don't always lyse |
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Limits of automated flow cytometry counters (WOC)
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Need highly trained people
Platelet clumps counted as WBC More expensive nRBC counted as WBCs |
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Methods of manual WBC counts
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Hemacytometer
buffy coat estimates slide estimates most about 20% error |
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Primary granules (of granulocytes)
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present in all of them
Azurophilic develop in promyelocyte, but loose staining characteristics by myelocyte |
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Secondary granules (of granulocytes)
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Differentiate the neutrophil, Eo, and basophil
develop at the myelocyte stage |
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Elements of primary granules of neutrophils
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MICROBICIDAL
-myeloperoxidase, lysozyme, defensins, bactericidal permeability-inducing protein ENZYMES -acid hydrolases, neutral proteases, elastase |
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Elements of secondary granules of neutrophils
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MICROBICIDAL
-lactorferrin, lysozyme, cathelicidins ENZYMES -Alkanine phosphatase, collagenase, apolactoferin, C5a splitting enzyme |
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Function of neutrophils
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Phagocytic
Microbicidal -secrete substances for extracellular digestion, & stimulate further inflammatory mediators |
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Lymphocyte distribution & function
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Widely distributed-lymph nodes, spleen, thymus, tonsils, bone marrow
Function-Humoral & cell-mediated immunity |
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Monocyte/Macrophage function
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Phagocytosis of opsonized material
Ab-dependent cytotoxicity Modulators of inflammatory rxn |
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Monopoiesis
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Takes ~3 days to produce
short circulating lifespan long (years) lifespan in tissues |
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Eosinophil production
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takes 2-6 days to produce
lifespan ~1hr in circulation, ~ 6 days in tissues primarily found in skin, resp & GI tracts |
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Function of Eosinophils
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Hypersensitivity, allergic & parasitic infections
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Eosinophil specific granules
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Major basic protein
Eosinophil peroxidase Eosinophil cationic protein |
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Function of Major basic protein
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in Eos
Cytotoxic to parasites, protozoa, bacteria |
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Function of Eosinophil peroxidase
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generates oxygen radicals in presence of H2O2, toxic to helminths, bacteria, fungi
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Function of Eosinophil Cationic protein
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Toxic to helminths, protozoa, bacteria
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Basophil production
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Controlled by IL-3
Production takes 3-5 days lifespan-0.5-6 hours in circulation, ~2 weeks in tissues |
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Function of basophils
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Primary role is in Type I hypersensitivity rxns
-hives, allergic rhinitis, conjunctivitis, asthma, parasites |
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Elements of Basophil granules
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Biogenic amines
Enzymes Proteoglycans Major Basic Protein |
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Biogenic amines of basophils
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Histamines
adenosine serotonin |
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3 Classifications of causes of Neutrophilia
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1. Excitement/Epinephrine
2. Stress/Cortisol 3. Inflammation |
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Constellation of data for an excitement (epinephrine/ physiologic) neutrophilia
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Mild Leukocytosis
Mature neutrophilia (no left shift) Lymphocytosis Erythrocytosis Thrombocytosis |
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Mechanisms of Epinephrine erythrocytosis/thrombocytosis
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REDISTRIBUTION
Splenic contraction marginal pool-into circulation increases hematocrit increases O2 carrying capacity makes more platelets available transient ~20 minutes |
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Constellation of data for a stress leukogram
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Leukocytosis
Neutrophilia Mild/insignificant left shift Lymphopenia +/- Monocytosis Eosinopenia |
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Causes of Stress leukogram
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Corticosteroid release due to:
-severe stress (physical/emotional) -Hyperadrenocorticism -Iatrogenic administration |
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Kinetics of Stress Leukogram
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Decreased margination
Increased bone marrow release (from storage pool) |
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Effect of Corticosteroids on Marginated Pool of neutrophils
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Decrease adhesion molecules
Neutrophils re-enter circulating pool & circulate longer (hypersegmentation) |
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3 Courses of inflammatory diseases
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1. Acute
2. Established 3. Chronic |
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Constellation of Data for Acute Inflammation
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Neutrophilia
Left shift -significant & orderly Lymphopenia Eosinopenia |
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Definition of a clinically significant left shift in:
a. Small animals b. Large animals |
a. > 1,000 bands
b. > 300 bands indicitive of significant inflammation |
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Regenerative/Appropriate Left Shift
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Segs outnumber bands
no more immature neutrophils in circulation |
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Definition of a clinically significant left shift in:
a. Small animals b. Large animals |
a. < 1,000 bands
b. < 300 bands indicitive of stress or chronic inflammation |
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Significance of a regenerative left shift
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moderate shift
segs outnumber bands Favorable prognosis-indicates bone marrow keeping up w/ demand |
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Neutrophil Kinetics of Acute Inflammation
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↑ Neutrophil release
↑ Neutrophil activity ↑ adherence to endothelium NO REDISTRIBUTION 5 day supply quickly depleted causing shift to immaturity |
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Response of the Bone Marrow during Acute Inflammation
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Storage pool empties,
then maturation pool release Oldest out first ↑ granulopoiesis |
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Response of the Bone Marrow during Established Inflammation
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Expansion (hyperplasia) of proliferating pool, catches up with demand allows Nonproliferating pool to repopulate, see less of a left shift
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Constellation of Data for Established inflammation
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Neutrophilia
Significant left shift -less shifted than acute Lymphopenia Monocytosis Eosinopenia |
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Constellation of Data for Chronic Inflammation
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Hyperplastic marrow
Mild neutrophilia -little/no left shift Normal->lymphocytosis Monocytosis NO REDISTRIBUTION |
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Kinetics of Neutrophils in Chronic Inflammation
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Continued demand for phagocytosis, time allows marrow to production to catch up with demand=no left shift, hyperplastic marrow
NO REDISTRIBUTION |
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Timeline for classification of inflammation
a. Acute b. Established c. Chronic |
a. 0-3 days
b. 4-6 days c. > 7-10 days |
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Data similarities between stress & chronic inflammation
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leukocytosis
neutrophilia no/insignificant left shift monocytosis |
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Differences to look for the tell between stress & chronic inflammation
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stress=lymphopenia
chronic inflammation=normal-> lymphocytosis |
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Other indicators of inflammation
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↑ globulins
↑ rouleaux ↑ acute phase proteins neutrophilic toxic change |
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Etiology of Neutrophilic toxic change
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Accelerated granulopoiesis causes defects in granule maturation in the marrow (doesn't occur in circulation)
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Causes of neutrophilic toxic change
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usually- marked inflammation
paraneoplastic recombinant Colony Stimulating Factor Therapy |
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Signs of toxic change
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Dohle bodies
Cytoplasmic basophilia vacuolation (foaminess) Toxic granulation (of primary granules) Giant cells Hyposegmentation IN ORDER OF SEVERITY |
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Cause of Dohle body formation
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Lamellar RER aggregates
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Cause of Cytoplasmic basophilia
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RER
RNA (polyribosomes) retention |
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Causes of vacuolation
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Autodigestion, fluid accumulation
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Causes of toxic granulation
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Primary granules pick up stain again
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When to give an unfavorable (guarded) prognosis based on WBCs
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Degenerative left shift
Leukemoid response Neutropenia |
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Definition of a degenerative or inappropriate left shift
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Degenerative- leukocytosis, w/ bands outnumbering segs
inappropriate- neutropenia/ low end of RI, & significant left shift |
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What is a leukemoid response?
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Profound neutrophilia (40-50K)
shift back to myelocytes Neutrophilia is ineffective guarded-poor prognosis differentiate from chronic granulocytic leukemia |
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What are the 3 mechanisms of neutropenia?
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-Excessive tissue demand
-Sequestration -Reduced production |
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When to worry about neutropenia?
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<2,000-concerned
<1,500-worried <1,000-crisis |
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Mechanisms of increased tissue demand neutropenia
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severe inflammatory response
depletes marrow 5 day supply marrow is overwhelmed need to intervene degenerative left shift common |
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Mechanisms of sequestration neutropenia
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A psuedoneutropenia
REDISTRIBUTION to marginal pool=same total number in body less important Endotoxemia, anaphylaxis |
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Causes of reduced production neutropenia
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Hypoproliferative diseases
-viral -rickettsial -toxins -drugs -radiation |
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Aplastic pancytopenia
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Hypocellular bone marrow
decreases in all cell lines |
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Myelophthisic diseases
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Normal hematopoietic tissue replaced
-neoplasms, myelodysplasia, myelofibrosis, osteopetrosis causes cytopenias in mutliple (but not necessarily all cell lines) |
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When you need to sample the bone marrow?
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Persistent neutropenia, nonregenerative anemia, thrombocytopenia or pancytopenias
Dysplastic/neoplastic cells in circulation To stage other neoplasms --lymphosarcoma, Mast cell |
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What you need with a bone marrow sample?
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CBC w/in 24 hours
Blood smear Marrow smear from aspirate Core biopsy |
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What to look for with a smear of a bone marrow aspirate?
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Overall cellularity
M:E Maturation of each cell line -proportionate -morphology |
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What cells in circulation still have mitotic potential?
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Lymphocytes
Monocytes (to limited degree) |
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Definition of Myelopoiesis?
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Production of all the cell lines from bone marrow:
RBC's, platelets, & all WBC's EXCEPT LYMPHS |
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Lymphopoiesis
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Begins in the marrow
majority takes place in extramedullary lymphoid tissue lymph node, thymus, spleen, BALT, GALT |
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What are the 2 manifestations of hematopoietic neoplasia?
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Sarcomatous masses (tumors of connective tissue)
Leukemia (disseminated neoplasia) |
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Characteristics of bone marrow in myelophthisic disease
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Hypercellular
Abnormal/neoplastic cells very few normal cells present |
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What are the 3 different kinds of leukemia?
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Aleukemic leukemia
subleukemic leukemia leukemic leukemia |
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Characteristics of Aleukemic leukemia
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Very Early in Disease process
No neoplastic cells in circulation, restricted to the bone marrow Rarely diagnosed @ this stage |
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Characteristics of subleukemic leukemia
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Early in disease process
Few neoplastic cells found in circulation, but not enough to cause a leukocytosis |
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Characteristics of Leukemic leukemia
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Vastly increased neoplastic cells in circulation
Easily diagnosed |
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Complications due to leukemia
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Secondary infections
-from neutropenia Hypoxia -from anemia/hyperviscus Hemorrhage -from thrombocytopenia Organ failure -from infiltration of neoplastic cells |
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Characteristics of Acute Leukemia
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Rapid onset
Cellular immaturity -BLASTS/other precursors in circulation -difficult to ID cell lines Short survival time |
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Characteristics of Chronic Leukemia
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Prolonged course
Cellular maturity -can tell what cells are -but cells are abnormal:giantism, abnormal segmentation, altered chromatin patterns |
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2 Classifications of Hematopoietic neoplasia based on cell types
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Myeloproliferative
-stuff made in bone marrow Lymphoproliferative -lymphoid cells |
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Cell lines of Lymphoproliferative neoplasia
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T-lymphocytes
B-lymphocytes Plasma cells NK cells |
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Acute lymphocytic leukemia
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Originate in the bone marrow
neoplastic, BLAST cells in circulation |
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Chronic lymphocytic leukemia
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Originate in the bone marrow
abundant, differentiated cells in circulation |
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Characteristics of Lymphosarcomas
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Sarcomatous masses of:
lymph nodes spleen GI tract skin may see a secondary leukemia late |
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Characteristics of Plasma cell tumors
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Myelomas (sacromas)
Originate in the marrow -bone lysis -monoclonal hyperglobinemia -<5% in marrow -Bence Jones protein in urine |
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What are Bence-Jones proteins?
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Free immunoglobulin chains that readily pass through glomerulus into urine
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Characteristics of Acute Red Cell Neoplasia
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Erythremic Myelosis (seen in FeLv positive cats)
Nonregenerative anemia ↑MCV ↑#nRBC Giant platelets |
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Characteristics of Chronic Red Cell Neosplasia
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(Polycythemia Vera)
Cells look normal on slide but Hct is way too high ~75% |
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Relative Polycythemia
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Total RBC mass is normal
-hemoconcentration due to decreased plasma volume (usually dehydration-↑ PP) -Excitement-causing splenic contraction (mainly in horses) |
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Absolute polycythemia
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↑ in total RBC mass
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Secondary Absolute Polycythemia
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due to an increase in Epo
can be appropriate: due to hypoxia, high altitudes or inappropriate: Epo being secreted but isn't needed (Epo secreted tumors) |
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Primary Absolute Polycythemia
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Epo normal/decreased
=chronic RBC leukemia (other cell lines not effected) true myeloproliferative disease normal pO2 |
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Essential thrombocythemia
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Chronic platelets leukemia
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Acute myelomonocytic leukemia
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Blast stages in circulation
w/ increased #'s of differentiated mono's & neutrophils derived from same progenitor cells |
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Chronic Myelomonocytic leukemia
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↑ numbers of dysplastic differentiated mono's & neutrophils
both derived from the same progenitor cells |
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What is a leukemoid left shift?
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Pronounced neutrophilia
w/ left shift (40-50K+)-possible to see shift back to myelocyte stage Guarded to poor prognosis |
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How to tell the differences between a leukemoid left shift & Chronic granulocytic leukemia?
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Leukemoid=orderly left shift
Chronic granulocytic leukemia= disordered left shift |
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When to give a poor prognosis?
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Neutropenia (except ruminants)
Leukemoid left shift Left Shift -degenerative -or w/neutropenia -back to proliferating pool Degenerative left shifts/neutropenia in ruminants for >4 days |
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Significannceor Reactive Lymphocytes
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Lymphs have been Antigenically stimulated
= immunocytes / atypical lymphs |
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Morphologic changes seen with reactive lymphocytes
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Small Lymphs:
-↑Cytoplasmic basophilia -↑Cytoplasm Large Lymphs: -↑Cytoplasm -↑ Cytoplasmic basophilia -+/- clear zone around the nucleus |
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Typical Leukocyte Responce in the cat
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Doehle bodies common
Less Monocytosis in responce to stress Marginal Neutrophil pool ~ 3X the circulating pool |
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Typical Leukocyte Responce in Ruminants
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Normally have 2x more lymphs than neutrophills.
Acute inflammation causes neutropenia w/ degenerative left shift. WBC counts ~20-30K very significant Fibrinogent, acute phase proteins better indications of inflammation than WBC count |
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Typical Neutrophil Responces in Ruminants
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Neutropenia w/acute inflammation
-Small / no storage pool in marrow -Marrow responds poorly Toxic changes common Young calves - essentially monogastric, so similar leukocytes responses as dogs |
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Typical leukocytes responce in Horse
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Kinetics similar to the dog, but:
lower #'s indicative of inflammation ~15-20k = moderate inflammation 20-30k = significant |
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Most common cause of Lymphopenia
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Corticosteroids
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Significance of Monocytopenia?
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no specific significance
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Role of T-Lymphocytes
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circulate in blood + lymph nessels important for immune surveillance
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Role of B-lymphocytes
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Reside in secondary lymphoid tissue
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Effect of Acute stress/inflammtion on lymphocytes counts
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Trap T-cells in lymphatics ↓ # in circulation(REDISTRIBUTION)
=lymphopenia |
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Effect of chronic stress or high corticosteroids on lymphocytes counts???
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causes lysis of lymphocytes in the thymus + lymphnodes
=lymphopenia |
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Effect of Epinephrine on lymphocytes counts
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Thoracic duct emties into circulation,
↓ blood through lymph nodes =transient ↑ in lymphocytes # |
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4 causes of lymphopenia
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1.Loss/blockage of lymp flow
2.Impaired lymphopoiesis 3.Stress/steroids 4.Acute infection |
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6 causes of lymphocytosis
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1.Epinephrine/excitement
2.Chronic inflammation 3.Post vaccination (4-14 days) 4.Neoplasia 5.Species differences Swine + Rodents have ↑ 6.Age: ↑ in young |
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Neoplastic causes of lymphocytosis
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Persistent lymphocytosis occurs in cattle
-subclinical BLV infection Leukemia Leukemic phase of lymphosarcoma |
