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245 Cards in this Set

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Test sensitivity
No false negatives
the ability of a test to identify disease in diseased animals
If diseased, must be positive
Test specificity
No false positives
the ability of a test to identify health in healthy animals
If no disease, must be negative
Positive predictive value
The probability of an animal with a positive test result actually has the disease
Negative predictive value
The probability of an animal with a negative test result actually does not have the disease
Influences of predictive value
Disease prevelance has strong affect on predictive value: higher prevelance, greater predictive value
Significance of Test bias
=Accuracy/systemic error

how close the test result is to the true value
Significance of Precision
=CV/ Random error

How reproducible the test results are
Requirements of a "good test"
Test Bias
Precision
Primary Urinary profiles
BUN
Creatinine
UA
-physical, chemical, sediment
Secondary Urinary profiles
Electrolytes
Acid-Base profile
Primary Liver profile for LA
AST
SDH
GGT
ALP
Bilirubin
Secondary Liver profile for LA
Glucose
BUN
Cholesterol
Protein
Primary Liver profile for SA
ALT
AST
ALP
GGT
Bilirubin
Secondary Liver profile for SA
Glucose
BUN
Protein
Cholesterol
Fluid/electrolytes profile
Serum Profile
Hematocrit
BUN, Creatinine, Urine S.G.
Electrolytes
Acid-base profile
Muscle Profile
CK
AST
Potassium
Myoglobinemia/uria
Primary Pancreas/Carb profile
Glucose
UA-glucose, ketones
Secondary Pancreas/Carb profile
Acid-base profile
liver profile
electrolytes
amylase/lipase
Gastrointestinal profiles
Serum proteins
Electrolytes
Acid-base
electrolytes
Two types of marrow
Red=hematopoietic
Yellow=adipose
Sites of marrow hematopoietic activity
all bones in young animals
flat bones & epiphysis of long bones in older animals
Multipotential stem cells
look like small lymphocytes
divide & replace themselves & to produce differentiated/ committed progenitor cells
Growth factors influencing hematopoiesis
IL-3, Granulocyte-macrophage colony stim. factor (GM-CSF),
Granulocyte-CSF
Stem Cell Factor
Erythropoietin
Thrombopoietin
Effect of IL-3 on hematopoiesis
it's a multipotential CSF
made by T lymphs
-supports growth of stem cells
& committed precursors
Effect of Granulocyte-Macrophage colony stimulating factor (GM-CSF)
made by T cells, endothelial cells & fibroblasts
-supports growth of CFU-GM, BFU-E & CFU-Meg
Effect of Stem Cell Factor
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
Effect of Granulocyte-colony stimulating factor (G-CSF)
made by T cells, endothelial cells & fibroblasts
-supports the terminal differentiation of neutrophils
Effect of Erythropoietin
Made in kidney
-supports BFU-E, CFU-E and the terminal differentiation of erythroid cells
Effect of Thrombopoietin
Made in liver & kidney
-regulated by mature platelets
-stimulate BFU-MK to proliferate & differentiate
-cause megakaryocytes to enlarge, endoreduplication & release proplatelets
Normal erythropoiesis
balanced replacement of RBCs lost in health (1%/day)
4 divisions=16 RBCs (rubricytes)
takes 5 days from stem cells to retic release
Stages of RBC maturation
Rubiblast
Prorubricytes
Rubricyte
Metarubricyte
Retic
Erythrocyte
Hemoglobin concentrations increases from early Rub. to late Rub.= shuts off division
Metarubricytes
Small, pyknotic nucleus-ready to extrude
Reticulocytes
Nucleus already extruded, but still contains RNA & organelles
Released in marrow sinus (-EQ)
Take another 24 hours to mature
Staining Retics
Wrights stain=polychromatophil
NMB=retic
Rubriblast
1st morphologically identified erythroid cell
big, round nucleus
single nucleolus
Characteristics of mature erythrocyte
No DNA/RNA
Fully hemoglobinized
Average RBC lifespan
-in dog
-in cat
-in horse
-in cow
dog-110
cat-70
horse-145
cow-150
Control of heme synthesis
Aminolevulinic acid synthetase
Porphyrins
Aminolevulinic acid synthetase
The rate limiting step of Heme synthesis
under negative feedback control from [heme] in RBC
Sensitive to Lead toxicosis
Significance of Porphyrins
Intermediates of heme biosynthesis
deficiencies of the enzymes in this pathway can cause disease
Functions of RBCs
Oxygen delivery to tissues
CO2 transport
H+ buffering
Maintain vascular integrity
-NO, ADPase, adenine nucleotides
Coagulation
Important pathways in erythrocyte metabolism
Embden-Meyerhof pathway
Hexose-monophosphate pathway
Methemoglobin reductase
Leubering-Rapoport pathway
Significance of Embden-Meyerhof Pathway
generates ATP & NADH
Significance of Hexose-monophosphate pathway
Prevents oxidative injury to RBCs
Significance of Methomoglobin reductase pathway
Keeps hemoglobin in reduced (Fe2+) form
Significance of Luebering-Rapoport Pathway
forms 2,3 DPG
-causes a right shift in oxygen dissociation curve
Mechanism of Extravascular hemolysis
Primary mechanism for removal of RBCs from circulation
RBCs are phagocytized by macrophages
Macrophage processing of Hemoglobin molecule
Hemoglobin is broken down to Heme & Globin
Globin→amino acids→reutilized
Heme→unconj. bilirub + albumin→ liver→ conjug. bilirub→ bile→ intestines
Mechanisms of intravascular hemolysis
a minor route of removing RBCs
RBCs lyse in ciculation, spilling Hb
Hb & haptoglobin→picked up and processed by hepatic macrophages
Overload of the Haptoglobin recovery system
Hb oxidized to MetHb (Fe3+)→free heme (Fe3+)→ complexed by hemopexin→liver→bile
prevents renal damage by heme
Purpose of Haptoglobin
to bind free hB in circulation, preventing it from being lost (via urine)
Definition of Hematology
Study of the nature & disease of blood & blood forming organs
Definition of Clinical Hematology
Utilize information derived from the study of blood, to diagnose & treat disease
Constituents of Serum
Red Top
centrifuged liquid portion of blood after it clots
Constituents of Plasma
Green (blue, purple) top
centrifuged liquid portion of blood with anticoagulant (no clotting)
Contains Fibrinogen & Coagulation proteins
Plasma Proteins
Albumin
Globulins
-immunoglobulin
-transport proteins
-acute phase proteins
-coagulation proteins
Plasma electrolyte cations
Sodium
Potassium
Calcium
Magnesium
Plasma electrolyte anions
Chloride
Bicarb
Phosphate
Sulfate
Mechanisms of anticoagulants
EDTA-Chelates calcium
Heparin-Activates antithrombin III
Citrate
Oxalate
Compensatory mechanisms for anemia
↓O2 affinity for Hb
-2,3 DPG-shift dissociation curve to the right
vasodilation-↑tissue perfusion
↑CO
↑Respiratory rate
↑RBC production
-via erythropoietin
What mechanisms cause Hct, Hb, and RBC numbers to ↑?
Polycythemia
-primary-increased production
-relative (dehydration)
What mechanisms cause Hct, Hb, and RBC numbers to ↓?
Anemia
Overhydration
Determining severity of anemia
Must consider hydration status
-do before giving fluids
-use PP to assess
Assessing anemia in dogs using PCV
30-37%=mild
20-29%=moderate
13-19%=severe
Assessing anemia in cats using PCV
20-26%=mild
14-19=moderate
10-13=severe
Causes of Macrocytic, Hypochromic anemias
REGENERATIVE
-hemolytic
-blood loss
Causes of Normocytic, Normochromic anemias
NON-REGENERATIVE
-Reduced erythropoiesis
-Ineffective/Defective erythropoiesis
Characteristics of Hemolytic anemias
REGENERATIVE
Macrocytic, Hypochromic
IMHA
Oxidative injury
Metabolic
Parasitic
Drug-induced
Characteristics of Blood loss anemias
REGENERATIVE
Macrocytic, Hypochromic
Internal and/or external losses
Characteristics of Reduced erythropoiesis anemias
NON-REGENERATIVE
Anemia of chronic Dz
Lack of erythropoietin
FeLV
Iron deficiency
Red cell aplasia
Characteristics of infective/defective erythropoiesis
NON-REGENERATIVE
normocytic, normochromic
Aplastic anemia
Myelophthisic anemia
Microcytosis
RBCs smaller than normal
due to decreased Hb synthesis
allows extra division of rubricytes
Factors causing ↓ in MCV
Iron deficiency
Portosystemic shunts
Akita/Asian breeds
What is MCH?
Mean corpuscular hemoglobin
average concentration of hemoglobin in a RBC in picograms (not used as much as MCHC-more accurate)
Factors causing ↓ in MCHC
RETICULOCYTOSIS
Iron deficiency
Factors causing false ↑ in MCHC
in vitro/vivo hemolysis
-lipemia
-hienz bodies
-oxyhemoglobin
-marked leukocytosis
-marked hyperproteinemia
Canine Reticulocytes
~1% normally in health
mature to in about 24 hours
Count all seen
Feline Reticulocytes
~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
Reticulocyte Production Index
Exaggerates the retic %
Accounts for immature retics staying in circulation longer than normal
Corr. retic x 1/matur. time
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
Absolute retic count
Best indicator of bone marrow production
but requires RBC count
=Retic % x RBC count
Effect of Reticulocytosis on CBC parameters
MCH
MCHC
MCV
MCH~normal
MCHC-decreased
MCV-increased
Ability of different species to respond to anemias
Dog-greatest ability
cat
cow
horse-least ability
Significance of nRBCs in circulation
Should be associated with reticulocytosis
Abnormal causes of nRBCs in circulation
Splenectomy
Bone marrow stromal damage
extramedullary hematopoiesis
lead toxicity
bone fracture
leukemia
corticosteroids
Change to microenvironment of hematopoietic organs
What is anisocytosis?
Variation in RBC Size
normal in cats & cows
Slide indications of Regenerative anemia
Polychromasia
Anisocytosis
+/-nRBC
+/-Howell-Jolly bodies
+/-basophilic stippling
Indications of Regeneration from CBC data
↓MCHC
↑MCV
↑RDW
↑Retic count/%
↑#nRBCs
What are the 3 Major classes of Anemic causes?
Loss of RBC-hemorrhage
Destroy RBC-hemolysis
Don't make RBC-production failure
Characteristics of acute hemorrhage
Cells, plasma & protein all lost in equal portions
Hct remains the same initially
Effect of Epinephrine release
Causes splenic contraction
-massive release of RBC, WBC & platelets
Hct up to 80%
Initial response to acute hemorrhage & CBC changes
Fluids move from interstial tissue to intervascular space
dilutes cells & proteins= anemia & hypoproteinemia
Retic/polychromasia=2-3 days
Reticulocytosis after acute blood loss
response take 2-3 days to develop
maximum response in 5-7 days
resolves in 1-2 weeks
Characteristics of Chronic hemorrhage
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
Characteristics of Iron Deficiency Anemia
Decreased Hb production
-Rubricytes take longer to reach critical levels, undergo extra division=small RBCs & ↑ central pallor
=microcytic, hypochromic
Non/poorly responsive
Constellation of Data for
Chronic Hemorrhage
Anemia
-increasingly microcytic
-hypochromic
-less regenerative
-schistocytes
Panhypoproteinemia (A:G=1:1)
Thrombocytosis
Characteristics of Extravascular hemolysis
↑ RBCs phagocytosis by macrophages in spleen/liver
-usually marked w/antibody or RBC parasite
Typical CBC data of Hemolytic anemia
+ Coombs test (direct agglutination)
Autoagglutination
Spherocytes
Leptocytes
Hyperbilirubinemia
+++Reticulocytosis
What are Leptocytes? & what do they signify?
Target cells
common in responding (hemolytic) anemias due altered membrane:lipid with skipped division during maturation
Macrophage digestion of hemoglobin
scavenge Fe to allow for more immediate reutilization
Heme is converted to bilirubin to be processed by the liver
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
Constellation of Extravascular hemolysis
Chronic insidious onset
Regenerative response
Increased (or normal) PP
+/- hyperbilirubinemia
Key distinguishing feature of intravascular hemolysis?
what to look for to know?
Hemoglobinemia
+/- hemoglobinuria
Hyperbilirubinemia- days later
Bilirubinemia
Hyperchromic-↑MCHC, Hb
Significance of Hemoglobin recovery system
Fe toxic to kidney b/c causes redox rxn in tubules
Need to conserve Fe, b/c only limited supply
Signs of hemoglobinemia
hemoglobinuria
brownish-red serum
Unconjugated Bilirubin
insoluble in water
what is initially released, with RBC lysis
Measured as indirect bilirubin
Conjugated Bilirubin
water soluble
what is released after being processed by the liver
Measured as direct bilirubin
Causes to Heinz body formation
Onions, garlic
Acetominophen
Red maple toxicosis
Copper, zinc
Diabetes mellitus
hyperthyroidism
10% normal in cats
Phenothiazine
Significance of the presence of Heinz bodies
Irreversible injury
-hemoglobin doesn't function
-causes membrane abnormality
weakened-lyse in circulation (seen as ghost cells)
Ghost Cells
Lysed RBCs with Heinz bodies weakening the membrane
How are Heinz bodies formed?
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
Heinz bodies in cats
~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
Fragmentation anemia
Intravascular strands of fibrin/altered vessels
-cleave RBCs
=schistocytes
What are schistocytes?
Fragments of RBCs
Irregular shapes
Seen w/ fragmentation anemias & iron deficiency anemias
Significance of Pyruvate Kinase Deficiency?
Impaired energy metabolism
causing premature RBC destruction
↑ 2,3 DPG-blood O2 saturation increases to compensate
-usually exercise intolerant
Signs of a pyruvate kinase deficiency
Moderate-severe anemia
Macrocytic, hypochromic
Marked reticulocytosis
No RBC morph changes
Signs of Phosphofructokinase deficiency
Persistent compensated anemia
PCV normal/slightly decreased
Moderate reticulocytosis
RBCs highly fragile
Parasitic causes of hemolytic anemia
Anaplasma
Babesiosis
Haemobartonella
Eperythrozoonosis
Sarcocytosis
Trypanosoma
Theileriosis
Cytauxzoonosis (cats)
Bacterial causes of hemolytic anemia
Lepto
-bacillary hemoglobinuria
Viral causes of hemolytic anemia
Equine Infectious Anemia
Mechanism of Anemia of Chronic disease
A production failure b/c iron is diverted to macrophages & hepatocytes, makes less available for hematopoiesis
Theory behind Anemia of Chronic Disease
A protective measure makes less iron available to bacteria
Characteristics of anemia of chronic disease
Moderate anemia (Hct~20%)
Normocytic, Normochromic
Anemia resolves when overlying condition resolved
Nonresponsive to iron injections
Anemia of chronic renal disease
Production failure
occurs when many nephrons are lost, erythropoeitin producing cells
Granulopoiesis
production of:
neutrophils
Eos
Basophils
(usually refer to neutrophils)
Bone marrow stromal cells
Fibroblasts
adipose
Macrophages
Monocytes
Lymphs
Products of Bone marrow stromal cells
Extracellular matrix proteins
Cytokines
inhibitory factors
adhesion molecules
Regulation of granulopoiesis by T-lymphocytes & macrophages
Growth factors
Colony stimulating factors
Lymphokines
Cytokines
Action of Colony stimulating factors
Increase/promote cellular function
stim. bone marrow release of neutrophils
promote neutrophil diapedeis
induce chemotaxis
enhance phagocytosis & microbicidal activity
Population of proliferating pool of neutrophils in bone marrow
Myeloblast
Promyelocyte
Myelocyte (3 stages)
4-5 divisions
Population of nonproliferating pool of neutrophils in bone marrow
=Maturation & Storage pools
Metamyelocytes
Band
Seg
No further division
~5 days supply in health
Peculiarities of cow nonproliferating pool
they don't have a storage pool, do have a maturation pool
Advantages of Automated counters
Saves time
More reproducible
(less error)
Disadvantages of Automated counters (in general)
Need trained operators
-Requires proper handling & analysis
-recognize abnormal findings & instrument malfunction
-conduct maintenance/troubleshoot
Limits of Impedance automated counters (WIC)
all nucleated cells counted as WBC
some platelets counted as RBCs
Platelet clumps counted as WBC
Leukocyte clumps undercounted
RBCs don't always lyse
Limits of automated flow cytometry counters (WOC)
Need highly trained people
Platelet clumps counted as WBC
More expensive
nRBC counted as WBCs
Methods of manual WBC counts
Hemacytometer
buffy coat estimates
slide estimates
most about 20% error
Primary granules (of granulocytes)
present in all of them
Azurophilic
develop in promyelocyte, but loose staining characteristics by myelocyte
Secondary granules (of granulocytes)
Differentiate the neutrophil, Eo, and basophil
develop at the myelocyte stage
Elements of primary granules of neutrophils
MICROBICIDAL
-myeloperoxidase, lysozyme, defensins, bactericidal permeability-inducing protein
ENZYMES
-acid hydrolases, neutral proteases, elastase
Elements of secondary granules of neutrophils
MICROBICIDAL
-lactorferrin, lysozyme, cathelicidins
ENZYMES
-Alkanine phosphatase, collagenase, apolactoferin, C5a splitting enzyme
Function of neutrophils
Phagocytic
Microbicidal
-secrete substances for extracellular digestion, & stimulate further inflammatory mediators
Lymphocyte distribution & function
Widely distributed-lymph nodes, spleen, thymus, tonsils, bone marrow
Function-Humoral & cell-mediated immunity
Monocyte/Macrophage function
Phagocytosis of opsonized material
Ab-dependent cytotoxicity
Modulators of inflammatory rxn
Monopoiesis
Takes ~3 days to produce
short circulating lifespan
long (years) lifespan in tissues
Eosinophil production
takes 2-6 days to produce
lifespan ~1hr in circulation, ~ 6 days in tissues
primarily found in skin, resp & GI tracts
Function of Eosinophils
Hypersensitivity, allergic & parasitic infections
Eosinophil specific granules
Major basic protein
Eosinophil peroxidase
Eosinophil cationic protein
Function of Major basic protein
in Eos
Cytotoxic to parasites, protozoa, bacteria
Function of Eosinophil peroxidase
generates oxygen radicals in presence of H2O2, toxic to helminths, bacteria, fungi
Function of Eosinophil Cationic protein
Toxic to helminths, protozoa, bacteria
Basophil production
Controlled by IL-3
Production takes 3-5 days
lifespan-0.5-6 hours in circulation, ~2 weeks in tissues
Function of basophils
Primary role is in Type I hypersensitivity rxns
-hives, allergic rhinitis, conjunctivitis, asthma, parasites
Elements of Basophil granules
Biogenic amines
Enzymes
Proteoglycans
Major Basic Protein
Biogenic amines of basophils
Histamines
adenosine
serotonin
3 Classifications of causes of Neutrophilia
1. Excitement/Epinephrine
2. Stress/Cortisol
3. Inflammation
Constellation of data for an excitement (epinephrine/ physiologic) neutrophilia
Mild Leukocytosis
Mature neutrophilia (no left shift)
Lymphocytosis
Erythrocytosis
Thrombocytosis
Mechanisms of Epinephrine erythrocytosis/thrombocytosis
REDISTRIBUTION
Splenic contraction
marginal pool-into circulation
increases hematocrit
increases O2 carrying capacity
makes more platelets available
transient ~20 minutes
Constellation of data for a stress leukogram
Leukocytosis
Neutrophilia
Mild/insignificant left shift
Lymphopenia
+/- Monocytosis
Eosinopenia
Causes of Stress leukogram
Corticosteroid release due to:
-severe stress (physical/emotional)
-Hyperadrenocorticism
-Iatrogenic administration
Kinetics of Stress Leukogram
Decreased margination
Increased bone marrow release (from storage pool)
Effect of Corticosteroids on Marginated Pool of neutrophils
Decrease adhesion molecules
Neutrophils re-enter circulating pool & circulate longer (hypersegmentation)
3 Courses of inflammatory diseases
1. Acute
2. Established
3. Chronic
Constellation of Data for Acute Inflammation
Neutrophilia
Left shift
-significant & orderly
Lymphopenia
Eosinopenia
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
Regenerative/Appropriate Left Shift
Segs outnumber bands
no more immature neutrophils in circulation
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
Significance of a regenerative left shift
moderate shift
segs outnumber bands
Favorable prognosis-indicates bone marrow keeping up w/ demand
Neutrophil Kinetics of Acute Inflammation
↑ Neutrophil release
↑ Neutrophil activity
↑ adherence to endothelium
NO REDISTRIBUTION
5 day supply quickly depleted causing shift to immaturity
Response of the Bone Marrow during Acute Inflammation
Storage pool empties,
then maturation pool release
Oldest out first
↑ granulopoiesis
Response of the Bone Marrow during Established Inflammation
Expansion (hyperplasia) of proliferating pool, catches up with demand allows Nonproliferating pool to repopulate, see less of a left shift
Constellation of Data for Established inflammation
Neutrophilia
Significant left shift
-less shifted than acute
Lymphopenia
Monocytosis
Eosinopenia
Constellation of Data for Chronic Inflammation
Hyperplastic marrow
Mild neutrophilia
-little/no left shift
Normal->lymphocytosis
Monocytosis
NO REDISTRIBUTION
Kinetics of Neutrophils in Chronic Inflammation
Continued demand for phagocytosis, time allows marrow to production to catch up with demand=no left shift, hyperplastic marrow
NO REDISTRIBUTION
Timeline for classification of inflammation
a. Acute
b. Established
c. Chronic
a. 0-3 days
b. 4-6 days
c. > 7-10 days
Data similarities between stress & chronic inflammation
leukocytosis
neutrophilia
no/insignificant left shift
monocytosis
Differences to look for the tell between stress & chronic inflammation
stress=lymphopenia
chronic inflammation=normal-> lymphocytosis
Other indicators of inflammation
↑ globulins
↑ rouleaux
↑ acute phase proteins
neutrophilic toxic change
Etiology of Neutrophilic toxic change
Accelerated granulopoiesis causes defects in granule maturation in the marrow (doesn't occur in circulation)
Causes of neutrophilic toxic change
usually- marked inflammation
paraneoplastic
recombinant Colony Stimulating Factor Therapy
Signs of toxic change
Dohle bodies
Cytoplasmic basophilia
vacuolation (foaminess)
Toxic granulation (of primary granules)
Giant cells
Hyposegmentation
IN ORDER OF SEVERITY
Cause of Dohle body formation
Lamellar RER aggregates
Cause of Cytoplasmic basophilia
RER
RNA (polyribosomes) retention
Causes of vacuolation
Autodigestion, fluid accumulation
Causes of toxic granulation
Primary granules pick up stain again
When to give an unfavorable (guarded) prognosis based on WBCs
Degenerative left shift
Leukemoid response
Neutropenia
Definition of a degenerative or inappropriate left shift
Degenerative- leukocytosis, w/ bands outnumbering segs

inappropriate- neutropenia/ low end of RI, & significant left shift
What is a leukemoid response?
Profound neutrophilia (40-50K)
shift back to myelocytes
Neutrophilia is ineffective
guarded-poor prognosis
differentiate from chronic granulocytic leukemia
What are the 3 mechanisms of neutropenia?
-Excessive tissue demand
-Sequestration
-Reduced production
When to worry about neutropenia?
<2,000-concerned
<1,500-worried
<1,000-crisis
Mechanisms of increased tissue demand neutropenia
severe inflammatory response
depletes marrow 5 day supply
marrow is overwhelmed
need to intervene
degenerative left shift common
Mechanisms of sequestration neutropenia
A psuedoneutropenia
REDISTRIBUTION to marginal pool=same total number in body
less important
Endotoxemia, anaphylaxis
Causes of reduced production neutropenia
Hypoproliferative diseases
-viral
-rickettsial
-toxins
-drugs
-radiation
Aplastic pancytopenia
Hypocellular bone marrow
decreases in all cell lines
Myelophthisic diseases
Normal hematopoietic tissue replaced
-neoplasms, myelodysplasia, myelofibrosis, osteopetrosis
causes cytopenias in mutliple (but not necessarily all cell lines)
When you need to sample the bone marrow?
Persistent neutropenia, nonregenerative anemia, thrombocytopenia or pancytopenias
Dysplastic/neoplastic cells in circulation
To stage other neoplasms
--lymphosarcoma, Mast cell
What you need with a bone marrow sample?
CBC w/in 24 hours
Blood smear
Marrow smear from aspirate
Core biopsy
What to look for with a smear of a bone marrow aspirate?
Overall cellularity
M:E
Maturation of each cell line
-proportionate
-morphology
What cells in circulation still have mitotic potential?
Lymphocytes
Monocytes (to limited degree)
Definition of Myelopoiesis?
Production of all the cell lines from bone marrow:
RBC's, platelets, & all WBC's
EXCEPT LYMPHS
Lymphopoiesis
Begins in the marrow
majority takes place in extramedullary lymphoid tissue
lymph node, thymus, spleen, BALT, GALT
What are the 2 manifestations of hematopoietic neoplasia?
Sarcomatous masses (tumors of connective tissue)

Leukemia (disseminated neoplasia)
Characteristics of bone marrow in myelophthisic disease
Hypercellular
Abnormal/neoplastic cells
very few normal cells present
What are the 3 different kinds of leukemia?
Aleukemic leukemia
subleukemic leukemia
leukemic leukemia
Characteristics of Aleukemic leukemia
Very Early in Disease process
No neoplastic cells in circulation, restricted to the bone marrow
Rarely diagnosed @ this stage
Characteristics of subleukemic leukemia
Early in disease process
Few neoplastic cells found in circulation, but not enough to cause a leukocytosis
Characteristics of Leukemic leukemia
Vastly increased neoplastic cells in circulation
Easily diagnosed
Complications due to leukemia
Secondary infections
-from neutropenia
Hypoxia
-from anemia/hyperviscus
Hemorrhage
-from thrombocytopenia
Organ failure
-from infiltration of neoplastic cells
Characteristics of Acute Leukemia
Rapid onset
Cellular immaturity
-BLASTS/other precursors in circulation
-difficult to ID cell lines
Short survival time
Characteristics of Chronic Leukemia
Prolonged course
Cellular maturity
-can tell what cells are
-but cells are abnormal:giantism, abnormal segmentation, altered chromatin patterns
2 Classifications of Hematopoietic neoplasia based on cell types
Myeloproliferative
-stuff made in bone marrow

Lymphoproliferative
-lymphoid cells
Cell lines of Lymphoproliferative neoplasia
T-lymphocytes
B-lymphocytes
Plasma cells
NK cells
Acute lymphocytic leukemia
Originate in the bone marrow
neoplastic, BLAST cells in circulation
Chronic lymphocytic leukemia
Originate in the bone marrow
abundant, differentiated cells in circulation
Characteristics of Lymphosarcomas
Sarcomatous masses of:
lymph nodes
spleen
GI tract
skin
may see a secondary leukemia late
Characteristics of Plasma cell tumors
Myelomas (sacromas)
Originate in the marrow
-bone lysis
-monoclonal hyperglobinemia
-<5% in marrow
-Bence Jones protein in urine
What are Bence-Jones proteins?
Free immunoglobulin chains that readily pass through glomerulus into urine
Characteristics of Acute Red Cell Neoplasia
Erythremic Myelosis (seen in FeLv positive cats)
Nonregenerative anemia
↑MCV
↑#nRBC
Giant platelets
Characteristics of Chronic Red Cell Neosplasia
(Polycythemia Vera)
Cells look normal on slide
but Hct is way too high ~75%
Relative Polycythemia
Total RBC mass is normal
-hemoconcentration due to decreased plasma volume (usually dehydration-↑ PP)
-Excitement-causing splenic contraction (mainly in horses)
Absolute polycythemia
↑ in total RBC mass
Secondary Absolute Polycythemia
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)
Primary Absolute Polycythemia
Epo normal/decreased
=chronic RBC leukemia (other cell lines not effected)
true myeloproliferative disease
normal pO2
Essential thrombocythemia
Chronic platelets leukemia
Acute myelomonocytic leukemia
Blast stages in circulation
w/ increased #'s of differentiated mono's & neutrophils
derived from same progenitor cells
Chronic Myelomonocytic leukemia
↑ numbers of dysplastic differentiated mono's & neutrophils
both derived from the same progenitor cells
What is a leukemoid left shift?
Pronounced neutrophilia
w/ left shift (40-50K+)-possible to see shift back to myelocyte stage
Guarded to poor prognosis
How to tell the differences between a leukemoid left shift & Chronic granulocytic leukemia?
Leukemoid=orderly left shift

Chronic granulocytic leukemia= disordered left shift
When to give a poor prognosis?
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
Significannceor Reactive Lymphocytes
Lymphs have been Antigenically stimulated
= immunocytes / atypical lymphs
Morphologic changes seen with reactive lymphocytes
Small Lymphs:
-↑Cytoplasmic basophilia
-↑Cytoplasm
Large Lymphs:
-↑Cytoplasm
-↑ Cytoplasmic basophilia
-+/- clear zone around the nucleus
Typical Leukocyte Responce in the cat
Doehle bodies common
Less Monocytosis in responce to stress
Marginal Neutrophil pool ~ 3X the circulating pool
Typical Leukocyte Responce in Ruminants
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
Typical Neutrophil Responces in Ruminants
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
Typical leukocytes responce in Horse
Kinetics similar to the dog, but:
lower #'s indicative of inflammation
~15-20k = moderate inflammation
20-30k = significant
Most common cause of Lymphopenia
Corticosteroids
Significance of Monocytopenia?
no specific significance
Role of T-Lymphocytes
circulate in blood + lymph nessels important for immune surveillance
Role of B-lymphocytes
Reside in secondary lymphoid tissue
Effect of Acute stress/inflammtion on lymphocytes counts
Trap T-cells in lymphatics ↓ # in circulation(REDISTRIBUTION)
=lymphopenia
Effect of chronic stress or high corticosteroids on lymphocytes counts???
causes lysis of lymphocytes in the thymus + lymphnodes
=lymphopenia
Effect of Epinephrine on lymphocytes counts
Thoracic duct emties into circulation,
↓ blood through lymph nodes
=transient ↑ in lymphocytes #
4 causes of lymphopenia
1.Loss/blockage of lymp flow
2.Impaired lymphopoiesis
3.Stress/steroids
4.Acute infection
6 causes of lymphocytosis
1.Epinephrine/excitement
2.Chronic inflammation
3.Post vaccination (4-14 days)
4.Neoplasia
5.Species differences
Swine + Rodents have ↑
6.Age: ↑ in young
Neoplastic causes of lymphocytosis
Persistent lymphocytosis occurs in cattle
-subclinical BLV infection
Leukemia
Leukemic phase of lymphosarcoma