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163 Cards in this Set

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Explain why RBCs rely on glycolysis for energy production
Glycolysis generates ATP as energy source and NADH as reducing agent in MetHg reductase pathway

because they are anucleate and have no organelles so no protein synthesis or oxidative phosphorylation

Still metabolically active for

Active transport

Maintain shape, deformability

*Minimize oxidative damage*
- MetHb reductase and Pentose Shunt
Define hematopoiesis
The formation, proliferation, and maturation of blood cells
define leukopoiesis
The formation, proliferation, and maturation of leukocytes

Includes granulopoiesis, lymphopoiesis, and myelopoiesis
define erythropoiesis
The formation, proliferation, and maturation of erythrocytes
define myelopoiesis
The formation, proliferation, and maturation of nonlymphoid leukocytes
Platelet production consists of ________ & ______
megakaryopoiesis and thrombopoiesis
The formation of platelets from megakaryocytes
All erythroid cells in an animal (includes precursors)
All leukocytes in an animal (includes precursors)
All megakaryocytes and platelets in an animal (includes precursors)
Hematopoiesis occurs primarily where

Where else can it occur?
In the bone marrow

Spleen, liver, kidney, and lymph nodes
______ refers to hematopoiesis that occurs in the spleen (or liver)
Extramedullary hematopoiesis
_______ are self-renewing cells that are common ancestors of all blood cells
hematopoietic stem cells
The main hematopoietic lineages in the bone marrow are _______
Erythroid, myeloid (nonlymphoid leukocytes, mainly neutrophils), and megakaryocytic
Where to T lymphocytes derive from
Bone marrow stem cells
The hematopoietic system is under _____ control
local and systemic
The marrow cavity is interlaced with venous sinuses composed of a luminal layer of ____ and an abluminal layer of _______

Where does hematopoiesis take place
Luminal layer of specialized endothelial cells

Abluminal layer of specialized fibroblasts known as adventitial reticular cells

Between these venous sinuses
What lines the venous sinuses of the bone marrow creating a barrier and regulating the traffic of cells and other substances b/w the intravascular and extravascular space
Sinusoidal endothelial cells along with their basement membrane
______ forms a scaffolding which supports the hematopoietic cells of the bone marrow
adventitial reticular cells
_____ are a major component of marrow tissue with increases in amount with age
fat cells
_______ provides structural support to the marrow via remodeling bone within the marrow space & likely contribute to regulation of hematopoietic stem cell proliferation and trafficking
Osteoblasts, osteoclasts, and elongated flat cells
_____ provide structural & biochemical support to the marrow to support the hematopoietic process
Specialized stromal cells (presumably of fibroblast origin)
What are the different stimuli that drive proliferation and maturation of the 3 main cell lineages of hematopoiesis
-Hypoxia detected by JG cells which produced EPO

-Inflammatory cytokines (IL-1, IL-6, and TNF-alpha)

Thrombopoiesis/ Megakaryopoiesis
-Thrombocytopenia results in increased plasma thrombopoietin levels
hypoxia has what effect on hematopoiesis
increases erythropoiesis

JG cells produce EPO
IL-6 has what effect on hematopoiesis
increases granulopoiesis
increased plasma thrombopoietin levels has what effect on hematpoiesis
increases thrombopoiesis
Hematopoiesis is subject to ______ kinetics (in health)
steady state kinetics
Give the general maturation times and life spans for neutrophils, platelets, RBC, lymphocytes (days/ weeks/ months/ years)
-Maturation: 7 days
-Survival: hrs

-Maturation: 2-10 days
-Survival: 5-10 days

-Maturation: 5 days
-Survival: 100 days

-Maturation: 7 days
-Survival: years (for some)
If a virus wiped out all of the early precursors, what cell lineage be depressed first on blood work
b/c survival is only hours
What is the dominant regulator of erythropoiesis

What is it and what effect does it have

A glycoprotein synthesized by renal juxtaglomerular interstitial cells which have an oxygen-sensitive hydroxylase

It promotes prolifieration and inhibits apoptosis of developing erythroid cells

Normally takes 5 days for a rubriblast to develop into a mature erythrocyte in circulation
What effect does hypoxia have on EPO production


What happens under normal conditions?
Up regulates it

Normal conditions
-Transcription factor (hypoxia inducible factor 1alpha) is hydroxylated which allows it to bind to a protein called von Hippel-Lindau protein which targets the HIF-1a molecule for degredation

In low oxygen tension (hypoxia)
-The hydroxylase is inactive so HIF-1a isn’t hydroxylated avoiding subsequent binding to VHL and degredation
-This promotes EPO gene expression
Granulopoiesis is regulated by what

Where does it come from

Normal maturation time
Many molecules including colony stimulating factors and interleukins

G-CSF is the primary regulator of neutropoiesis
- Produced by endothelial cells, fibroblasts, and macrophages in many tissues
- Production induced by inflammatory cytokines (IL-1, IL-6, and TNF-a)
- Promotes neutrophil production by increasing number of cell divisions and shortening the maturation time

Normal transit time from a myeloblast to release of a mature granulocyte into circulation is 7 days.
How are platelets formed
By fragmentation of cytoplasm from megakaryocytes

Regulated by thrombopoietin
- Synthesized in the liver (small amts made in kidney and skeletal muscle)
- When platelet mass decreased, less TPO bound to platelet receptors and the increased free TPO stimulates thrombopoiesis

Stromal cells in bone marrow increase production of TPO in states of severe thrombocytopenia

Hepatic expression of TPO can be increased by inflammatory mediators such as IL-6

Increases rate of formation/ release of platelets and increases mass
_______ is the primary regulator of neutropoiesis
granulocyte colony stimulating factor
define plasma

how do you collect it
the fluid (acellular) component of circulating blood

it is harvested after centrifugation of an anticoagulated blood sample
define serum
the fluid component of blood that is harvested after centrifugation of coagulated blood sampel

the same as plasma except that it lacks most coagulation proteins

the major protein that is absent in serum is FIBRINOGEN
how are plasma and serum different
plasma is collected from anticoagulated blood
- contains fibrinogen

serum is from coagulated blood
- lacks fibrinogen
_____ is the major protein which differentiates plasma from serum
- present in plasma (anticoagulated)
- not present in serum (coagulated)
what are the fxns of plasma proteins
- plasminogen

- IgM, IgG, IgA

inflamatory mediators
- complement
- C reactive protein

coagulation factors
- thrombin
- factor x

- glucagon
- insulin
- growth hormone

transport substances
- transferrin
- lipoproteins

- amino acids
______ is the principal force opposing the exit of fluid from the vascular system
colloidal osmotic pressure
decreased ______ results in edema
colloidal oncotic pressure
decreased _____ causes ascites
colloidal osmotic pressure
decreased ____ causes hydrothorax
colloidal osmotic pressure
decreased _____ causes increased total body water
colloidal osmotic pressure
_____ is the contribution to effective osmolality from macromolecules (mainly albumin)
colloidal osmotic pressure
changes in _____ cause sshifts between ECF and ICF
extracellular (serum) osmolality
extracellular (serum) osmolality
the number of solute particles per unit weight of serum

electrolytes and small molecules *such as glucose and urea* are the major contributors to the osmolality of serum
osmolality vs COP

which has proteins as a major contributor

which has electrolytes as a major contributor

extracellular (serum) osmolality
how do you determine serum osmolality
measured with osmometer or calculated from serum biochemistry panel

Osm = 1.86 ([Na] + [K]) + ([BUN]/2.8) + ([glucose]/18)

Na & K are in mEq/L or mmol/L

BUN & Glu are in mg/dl
rapid changes in _____ can cause cellular edema
extracellular (serum) osmolality
rapid changes in ______ can cause hemolysis
extracellular (serum) osmolality
What is the source of circulating proteins

1. albumin
2. B lymphocytes
3. alpha and beta globulins
4. coagulation factors (except VIII)
5. Coag Factor VIII
6. plasma cells
1. hepatocytes
2. lymphoid tissue
3. hepatocytes
4. hepatocytes
5. endothelial cells
6. lymphoid tissue
what are acute phase proteins?

where are they made?
alpha and beta globulins

made by hepatocytes
How do you measure total protein
biuret method
- colorimetric, spectrophotometric technique
- detects peptide bonds
- highly specific for protein measurement
- used on serum or plasma (g/dl)
- accurate for plasma, serum, body cavity effusions (when 1-10 g/dl)

precipitation and dye-binding methods
- quantify small amts of protein fround in urine/ CSF (mg/dl)

- changes in refractive index are proportional to protein concentration
- accurate when conc 1-10 g/dl
- usually used for plasma/ body cavity effusions
- specimen must be clear (lipemia/ hemolysis cause false increase)
- other solutes may affect refractive index of sample (glucose/ urea/ Na/ Cl) causing false increase
how do you measure albumin (g/dl)
Bromcresol green (BCG)
- dye binding method
- most used in vet labs
- note useful in birds/ reptiles (use serum or plasma protein electrophoreisis)

bromcresol purple (BCP)
- dye binding
- acurate in humans in human specimens only
- false low in animals
how do you measure globulin (g/dl)
TP-albumin = globulin

can be separated from albumin and directly quantified by serum protein electrophoresis

screening tests for failure of passive transfer of colostral antibody to foals and calves
- glutaraldehyde coag test
- zinc sulfate turbidity test
- latex agglutination
- membrane filter ELISA
how do measure for failure of passive transfer in calves/ foals
screening tests for failure of passive transfer of colostral antibody to foals and calves (globulins)
- glutaraldehyde coag test
- zinc sulfate turbidity test
- latex agglutination
- membrane filter ELISA
how do you measure fibrinogen (mg/dl)
heat precipitation method
- crude test
- usually done in conjuction with large animal CBC to screen for Hyperfibrinogenemia
- NOT sensitive enough to detect hypofibrinogenemia
______is the darkest band (and therefore the highest peak) for mammals on protein electrophoresis
what test is used to check for hypofibrinogenemia?

- (modified) thrombin time

- heat precipitation test
when would you want to use protein electrophoresis
evaluation of hyperglobulinemia
- monoclonal or polyclonal

evaluation of protein concentrations in birds and reptiles

6 regions in dogs and cats
- albumin
- alpha 1
- alpha 2
- beta 1
- beta 2
- gamma

4 regions in cattle
- albumin
- alpha
- beta
- gamma
what do you expect with each of the following protein abnormalities

1. Relative (dehydration)

2. Hyperalbuminemia

3. Hyperglobulinemia

4. Inflammation

5. Neoplasia

6. Hyperfibrinogenemia
1. relative (dehydration)
- water loss concentrates all plasma proteins proportionately
- increased TP
- increased albumin
- increased globulin
- increased hematocrit

2. hyperalbuminemia
- usually relative (dehydration)
- absolute increase rare (may occur with glucocorticoid administration due to increased albumin synethesis or life-span)

3. hyperglobulinemia
- upregulated during inflammation/infection
- increased [glob] due ti increased Ig's
- +/- acute phase proteins
- +/- complement

4. inflammation
- infectious or noninfectious (necrosis/ neoplasia/ immune mediated)
- Pos acute phase rxn
~hepatic synthesis of acute phase proteins increased w/in hrs of inflammatory stim and persist as long as stim present
~ alpha 1 & alpha 2 globulins
~ fibrinogen
~ serum amyloid A
~ C reactive protein (dogs)
- negative acute phase rxn
~ hepatic synthesis of neg acute phase proteins is decreased w/in days to weeks of inflammatory stimulus
~ albumin
~ transferrin
- delayed response
~ chronic stimulation causes increase in serum/plasma proteins in 1-3 weeks after onset of infammation
~ IgG
~ gamma-globulins
~complement (C3)
~ may see polyclonal gammopathy which may extend from gamma region to beta region (broad base)

5. neoplasia
- monoclonal gammopathy
- tall narrow peak in beta or gamma region

6. hyperfibrinogenemia
- inflammatory or neoplastic dz (fibrinogen is a pos APP)
- impt indicator of acute inflammation in cattle & horses
decribe the positive acute phase inflammatory reaction
APPs increased w/in hrs of inflammatory stim and persist as long as stim present
~ alpha 1 & alpha 2 globulins
~ fibrinogen
~ serum amyloid A
~ C reactive protein (dogs)
describe the negative acute phase inflammatory rxn
hepatic synthesis of neg acute phase proteins is decreased w/in days to weeks of inflammatory stimulus
~ albumin
~ transferrin
what do you expect to see in a protein electrophoresis if a plasma cell becomes neoplastic (myeloma)
monoclonal gammopathy
- tall, narrow spike in beta or gamma globulin region

need immunoelectrophoresis to identify Ig glass involved and confirm monoglonal gammopathy
what are the differentials for a monoclonal gammopathy
neoplasia of plasma cell (myeloma)

canine ehrlichiosis

canine leishmaniasis


(the last 3 are not true monoclonal gammopathy, they are restricted polyclonal or oligoclonal)
What would you expect to see with (and what are causes of)

1. relative (overhydration/ fluid retention)

2. Hypoalbuminemia
a. Increased loss from vascular space
b. decreased synthesis by liver

3. hypoglobulinemia

4. hypofibrinogenemia
1. relative (overhydration/ fluid retention)
- all plasma proteins diluted proportionately
- low TP
- low albumin
- low globulin
- see with overzealous IV fluid administration
- intersitial water shifts into plasma after acute blood loss
- with CHF

2. hypoalbuminemia
a. increased loss
- hemorrhage
~ HCT normal (initially)
~ HCT and plasma proteins decrease w/in 2-3 hrs as diluted by interstitial fluid
~ return to normal w/in 1 wk of resolution
- protein losing nephropathy
~ due to glomerulonephritis or renal amyloidosis
~ damage to glomerulus -> loss of negative charge across glomerular basement membrane -> allows albumin through (but not globulins) -> albumins lost in urine
- protein losing enteropathy
~ generalized SI mucosal or lymphatic dz (like, say, genetic freaks who don't know they're genetic freaks...) -> prohibits intestinal absorption and transport of proteins -> albumin and globulins lost in feces
- severe exudative skin dz/ burns
~ lose albumin and globulins

b. decreased synthesis
- hepatic insufficiency
~ < 20% functional mass remaining
~ chronic liver dzs (fibrosis/ chronic inflammation, portosystemic shunts, neoplasia)
- severe malabsorption/ maldigestion
~ increased protein catabolism -> fewer AA available for protein synthesis
~ generalized small intestinal dz or exocrine pancreatic insufficiency
- cachexia
~ due to chronic inflammation, neoplasia, starvation
- inflammation
~ albumin is neg acute phase protein
- plasma cell neoplasia (myeloma)
~ marked hyperglobulinemia -> increased COP -> down regulation of albumin production

3. hypoglobulinemia
- increased loss from vascular space
~ glob lost with albumin in hemorrhage, PLE, and exudation (not PLN)
- decreased Ig synthesis from lymphocytes
~ SCID of arabian or appaloosa foals or dogs (basset/ welsh corgi/ JRT) -> congenital failure to produce B an T lymphocytes -> no Ig produced
~ chemo
~ infections causing lymphoid hypoplasia (ex retroviral)
~ severe malabsorption, maldigestion, malnutrition (think of genetic freaks among you...)
- failure of passive colostral transfer
~ low gamma glob conc

4. hypofibrinogenemia (manifests as increased bleeding)
- DIC -> fibrinogen consumed
- congenital deficiency (rare)
in what situation would you expect albumin loss but no globuin loss
protein losing nephropathy

due to glomerulonephritis or renal amyloidosis

damage to glomerulus - > loss of neg charge across basemement membrane -> allows albumin through but not globulins (b/c they are too large)

albumin lost in urine
What do you expect protein values too look like with dehydration?
TP - increased
Alb - increased
Glob - increased
What would you expect the protein values to look like with chronic inflammation
TP - increased
Alb - normal to decreased
Glob - increased
What would you expect the protein values to look like with glomerular dz
TP decreased
Alb - decreased
Glob - normal
What would you expect protein values to look liek with failure of passive transfer
TP - decreased
Alb - normal
Glob - decreased
What would you expect protein values to look like with protein losing eneteropathy
TP - decreased
Alb - decreased
Glob - decreased
What would you expect protein values to look like with hemorrhage
TP - decreased
Alb - decreased
Glob - decreased
What would you expect protein values to look like in a Marsh Classification 3 Celiac patient (aka- severe villous blunting with no normal villi seen)
TP - decreased
Alb - decreased
Glob - decreased

b/c severe malabsorption
A heat precipitation test is used to detect what

(hyopfibrinogenemia is measured with a modified thrombin time)
3 classifications of anemia *and what they are characterized by (ie reticulocytosis or not)*
- no reticulocytosis

- impending reticulocytosis

- reticulocytosis
- except in those damn horses (b/c won't be there, except for when it is, b/c it's raining in the sudan)
how do mature RBC differ from reticulocytes
- smaller
- normal Hgb
- no RNA
- pink staining (normochromasia)
- neg NMB staining

- larger
- lower Hgb
- contains RNA
- purple staining (polychromasia)
- pos NMB staining
1. Are reticulocytes normally present in the circulation of

a. dogs & cats
b. cattle & other ruminants
c. horses

2. Are reticulocytes increased with regenerative resonse in

a. dogs & cats
b. cattle & other ruminants
c. horses
1. a. yes (low #s)
b. no
c. no

2. a. yes
b. yes
c. no (damn you Mr. Ed)
describe the anemia of inflammation
normocytic normochromic

decreased erythropoiesis
- functional iron deficiency (mediated by hepcidin)
~ high storage form of iron (fxnal sequestration) and low serum iron
- inhibition by other cytokines

shortened RBC life span
most regenerative anemias are _____ (Macro/normo/microcytic), ____ (macro/normo/ microchromic)

non-regenerative anemias?
- most are normocytic normochromic

- most are normocytic normochromic
- can be macrocytic hypochromic
describe hepcidin and its effect on inflammatory anemia
normall expression of hepcidin is low
- increased in inflammation

ferroportin normally expressed on cells *such as luminal GI tract cells & macrophages*
- allows iron inside cell to get out into the plasma
- it also serves as a receptor for hepcidin

when hepcidin binds, ferroportin is moved inside the cell and is degraded

get decreased iron absorption and decreased release of iron from storage

fxnal iron deficiency anemia
what is hepcidin's effect in a nutshell
inhibits intestinal absorption fo iron and release of iorn stored in macrophages
when do you see true iron deficiency?

what does it look like _____cytic, _____chromic anemia
in regenerative or nonregenerative anemia

usually secondary to chronic hemorrhage (esp GI)
- due to chronic loss of Hgb into extracellular environment
- HW
- intestinal neoplasia
- GI neoplasia

rarely due to nutritional deficiency (unless you have celiac's dz and can't absorb it from your diet)

microcytic, hypochromic anemia
- microcytosis develops first
is blood loss normall regenerative or nonregenerative

in the spirit of Dr. Henry, when is it not
normally regenerative

with the exception of iron deficiency b/c it can be regen or nonregen
why do you see anemia with CRF
decreased erythropoiesis

secondary to decreased EPO production by JG cells
how does thyroid fxn affect anemia?
- decreased erythropoiesis
- decreased EPO production
- decreased EPO responsiveness
- someone in our class is screwed, and it's not me :)

- 10-25% of peopole are anemic
- decreased erythrocyte survival?
- ineffective erythropoiesis?
- associated w/ increased Heinz bodies in cats (but not all affected cats are anemic)
- may cause erythrocytosis (secondary/ appropriate)
increased heinz bodies in cats are associated with

diabetes mellitus

hypoadrenocorticism (addison's dz) has what effect on erythropoiesis
decreased erythropoiesis

glucocorticoids interact with EPO and SCF to promote erythropoiesis

anemia may be masked by hypovolemia
- due to polyuria
- don't produce aldosterone normally

non-regenerative anemia
how does chronic liver dz affect erythropoiesis
non-regenerative anemai
- inflammation
- abnormal metabolism of AAs/ Proteins/ Lipids
- defective Fe handling

Portosystemic shunts
- often microcytic (mx not understood)
in what infectious diseases do you expect to see thrombocytopenia with anemia

EIAV (equine anemia virus)

infect erythropoietic cells
- direct suppression of early stage erythropoietic cells
- inflammation
- immune mediated hemolysis
FeLV (in relation to hemopoiesis)
causes wide spectrum of hematologic abnormalities

often macrocytic in the absence of reticulocytosis

subgroup C (uncommon) assoc with erythroid aplasia
Cat CBC shows macrocytosis (without normal pattern of macrocytic hyperchromic regenerative anemia). What is the dx
toxic injury to marrow shows what on CBC

give examples that could cause this
nonregenerative anemia

- generalized suppression of hematopoiesis

chemical agents
- chemo
- hyperestrogenism
- bracken fern toxicity

myelophthisis causes what kind of anemia


neoplasia (hematopoietic or metastatic)


replacement of hematopoietic tissue in marrow with other tissue (usually fibrous CT)
nonregenerative IMHA
prob occurs when erythroid cells destroyed before fully mature
- dx based on exclusion and response to therapy

bone marrow findings variable
- pure red cell aplasia (or very little erythropoiesis) to erythroid hyperplasia

most IMHA is regenerative
- but if targeting early stages (before mature) in bone marrow stage
- can see bone marrow with erythroid hyperplasia but it itsn't making it out into the periphery

it isn't the norm, but it is possible
name some (rare) causes of anemia

including nutritional (not iron) and congenital
nutritional deficiencies
- copper (disrupts iron metabolism)
- folate or cobalamin (B12) *nutritional or inherited*

congenital dyserythropoiesis
- Engl Springer Spaniels
- Polled Herefords
anemia in animals with neoplasia is most often ____ (regen/ nonregen)


disease related factors
- inflammation
- hemorrhage
- hemolysis (secondary IMHA)
- impaired renal fxn
- nutritional deficiencies
- myelopthisis

Tx related factors
- common complication of chemo/ radiation
- secondary hemolytic anemia (in people)

has a neg impact on quality of life, prognosis, and response to therapy

neoplasia can be regenerative (ala Henry)
describe erythrocytosis

what effect does it have on MCH/ MCHC
Increase in total number of RBC

not increase in Hgb so no increase in MCH/ MCHC
how will lipemia affect your CBC
falsely increased Hct (b/c degree to which light bends is not just due to protein but also to lipids)

false increase Hgb

MCH/ MCHC increased
define erythrocytosis
increased circulating RBC mass
what does the erythrogram show increases in for erythrocytosis
RBC (#/ul)

Hct (%)
- porportion of blood on volume displacement basis

Hgb (g/dL)
what are some non-pathologic causes of absolute erythrocytosis
breed variations



idopathic (mild)
what is relative erythrocytosis
not really more RBC, just looks like it

- dH2O
- endotoxemia (movement of water from intravascular to extravascular - not true dehydration)

redistribution of RBC
- splenic contraction (esp horses)
what are the causes of primary erythrocytosis
primary = non EPO dependent

polycythemia vera
- type of hematopoietic stem cell neoplasia

mutations affecting EPO receptor or transcriptional regulation of EPO
what are causes of secondary appropriate erythrocytosis
right to left shunts (hypoxia)

pulmonary dz (hypoxia)
- due to less oxygen exchange

- increased demand for O2
- direct effect of thyroid hormone on erythropoiesis?
- assoc with anemia?
appropriate vs inappropriated erythrocytosis
- increased EPO in response to decreased O2/ anemia
- increased RBC in 3-4 days (reticulocyte)
- normally takes 5 days to get reticulocyte into blood, but in the presence of EPO, there is a shorter transit time

- not in response to anemia/ hypoxia

malignant neoplasia

benign neoplasia
- collection of symptoms

malignant neoplasia
- characterized by spread (metastasis)/ invasion

benign neoplasia
- no metastasis or invasion
secondary inappropriate erythrocytosis causes
Renal lesions secreting EPO
- neoplasia
- cysts

extra-renal neoplasia secreting EPO
what are some non-pathologic causes of erythrocytosis (4)
breed variations



how do you diagnose the different types of erythrocytosis
- hx
- PE
- routine b/w
- dx straight forward
- plasma protein in tandem with PCV

2ary appropriate
- clinical signs
- lab data
- impaired oxygenation
- hyperthyroidism

other (exclusion/ additional testing)
- supports dx of 2 inappropriate:
~ renal or extrarenal tumor
~ high plasma [EPO]
- supports dx of primary
~ normal or decreased plasma [EPO]
hyperviscosity syndrome
increased viscosity, impaired blood flow, distention of microvasculature

increased risk of tissue hypoxia and thrombosis or hemorrhage

clinical signs
- erythematous mm
- prolonged CRT
- congested scleral or retinal blood vessels
- evidence of thrombosis or hemorrhage
- signs (eg neuro) related to affected organ system(s)
causes of regenerative anemia
blood loss

- immune mediated
- fragmentation
- infectious
- metabolic
- heinz body
what is the term for increased MCV?

decreased MCHC?
increased MCV
- macrocytosis

decreased MCHC
- hypochromasia
________ is almost always artifact (macrocytosis/ microcytosis/ hyperchromasia/ hypochromasia
most regenerative anemias are ___cytic, ____chromic
normocytic normochromic
what does an iron deficient anemia look like
microcytic, microchromic

microcytic, normochromic
agglutination has what effect on MCV
false increase
what 2 entities represent the same cell stained 2 different ways (Romanowsky & NMB) which represent regeneration
Romanowsky Stain
- polychromatophilic macrocyte

- Reticulocyte
______ is a visual suggestion that we have a regenerative anemia
what is the best way to determine if you have a regenerative anemia

how can you determine if you may have regeneration if all you have is a blood smear?

look for polychromasia

variation in cell size
suggestions of regeneration
polychromasia/ reticulocytosis

- variable size

Nucleated RBC
- metarubricyte

basophilic stippling
- usually only in ruminants with regen anemia
- presence of aggregated ribosomes on Romanowsky stained smear

howell-jolly body
- nuclear remnant
If you see a dog with nucleated RBC and basophilic stippling, what is your dx
lead toxicity (not regenerative anemia)
If you see a cow with nucleated RBC and basophilic stippling, what is your dx
regenerative anemia
When is rubricytosis appropriate?

rubricytosis = nucleated RBC present

- regeneration
- in presence of reticulocytes

- marrow damage (necrosis/ inflammation/ endotoxemia/ heat stroke/ neoplasia)
- extramedullary hematopoiesis
- splenic contraction or splenectomy
- lead poisoning with basophilic stippling
____ is THE BEST method for determining marrow response to anemia

what are the #'s for reference

how long does it take
Reticulocyte concentration/ count

dog = >80,000/ul
cat = >60,000/ul

takes 2-3 days after initiation of anemia
nucleated RBC (metarubricyte)

basophilic stippling
- presence of aggregated ribosomes on Romanowsky stained smear
- sign of regen in ruminant
- sign of lead poisoning in dog

- Look smaller
- No central pallor
- Be round

Halfway eaten cells
Sheared RBC (got clothes-lined by something)
- Altered vasculature
- Strand of fibrin from inflammation

RBC with at least 3 club shaped projections

Occur due to visceral problem (esp splenic/ hepatic)

May be pathognomonic in visceral hemangiosarcoma

Don’t mistake with Echinocytes/ crenation (spikey but not clubbed)
Echinocyte/crenation vs. Acanthocyte
Echinocytes/ crenation
- Spikey but not clubbed
- Rattle snake venom

- RBC with at least 3 club shaped projections
- Occur due to visceral problem (esp splenic/ hepatic)
Heinz Body

Aggregated denatured Hb

Blue on NMB

Clear on romanowsky stain

Often protruding from cell

- Never normal
- Due to oxidative damage

- See more often
evidence of hemolysis consists of
pre-hepatic hyperbilirubinemia and bilirubinruia
- overflow of unconjugated bilirubin from macrophages (conjugated in K9 kidney)
- overflow of conjugated bilirubin from liver
- results in bilirubinuria
hemolyzed plasma


erythrocyte chagned associated with causes of hemolysis
normal RBC breakdown/ bilirubin metabolism
In liver it is broken down into


- Broken down into Heme and biliverden

Biliverdin turned into unconjugated bilirubin
- Goes to blood
- Unconjugated bilirubin hooks up with albumin -> conjugated bilirubin
- Exits biliary tract
Hemolytic anemia findings
poikilocytosis or cell inclusions

neutrophilic leukocytosis


what does the CBC of a IMHA case look like
PCV down

HCT down

MCV up

MCHC normal

Reticulocytosis (uncorrected and corrected)

macrocytic normochromic regen anemia

Poikilocytosis or cell inclusions

Neutrophilic leukocytosis

Inflammatory leukogram +/-

Spherocytosis +/-

Agglutination +/-
what does the leukogram of a IMHA case look like
WBC up

Segs up

Bands normal

lymphs down

monos up
What is the horse’s HCT and TP minutes after the deep laceration is made? 12 hours? 5 days? 2 weeks?
evidence of hemolysis consists of
pre-hepatic hyperbilirubinemia and bilirubinuria

hemolyzed plasma


erythrocyte changes associated with causes of hemolysis
intravascular vs extravascular hemolysis
- Hgb - Released into plasma (red plasma in HCT tube)
- Freely filtered to urine

- pre-hepatic hyperbilirubinemia and bilirubinruia
- overflow of unconjugated bilirubin from macrophages (conjugated in K9 kidney)
- overflow of conjugated bilirubin from liver
results in bilirubinuria
What kind of bilirubin can be excreted in urine
conjugated bilirubin
prehepatic hyperbilirunemia causes
overflow of conjugated bilirubin from liver

overflow of unconjugated bilirubin from the macrophage
what do you see with IMHA
Poikilocytosis or cell inclusions

Neutrophilic leukocytosis



Inflammatory leukogram +/-

Spherocytosis +/-

Evans syndrome +/-

Agglutination +/-

Coombs’ Test positive +/-
signs of hemolysis (IV vs EV)

how does normal RBC breakdown/ bilirubin metabolism occur
- Hemoglobin released into plasma -> red plasma in HCT tube -> freely filtered into urine

- Pre-hepatic hyperbilirubinemia and bilirubinemia
• Overflow of unconjugated bilirubin from macrophages (Conjugated in canine kidney)
• Overflow of conjugated bilirubin from liver
• Results in bilirubinuria

• In liver, it is broken down into:
o Protein
o Hemoglobin: broken down into Heme and biliverdin
Biliverdin turned into unconjugated bilirubin-> goes to blood
o Unconjugated bilirubin hooks up with albumin -> conjugated bilirubin
- Exits biliary tract
causes of IMHA
Idiopathic or autoimmune

Drug induced

Isoimmune (NI)

Blood transfusion

held together by antibodies

formation due to reduction in membrane charge
IMHA CBC & Leukogram
o PCV down
o HCT down
o MCV up
o MCHC normal
o Retics up (uncorrected)
- Corrected: still up, regenerative
o Macrocytic, normochromic regenerative anemia

• Leukogram: inflammatory leukogram +/-
o WBC up
o Segs up
o Bands normal
o Lymphs down
o Monos up
IMHA blood smear
spherocytosis +/-, agglutination +/-

Hemolysis, icterus, spherocytes, clumping of RBCs

• Agglutination: antibodies are holding RBCs together

• Rouleaux: formation due to reduction in membrane charge
o Normal in horses and cats
o Will disperse when saline is added (“stack of coins”)
Signs of IMHA
o Fever
o Anorexia
o Weakness
o Prolonged CRT
o MM pale and icteric
Mechanism of IMHA
Macrophages get a little premature w/hemolysis, release inflammatory cytokines

 Leads to leukocytosis and presence of spherocytes

 Activates C’, leads to IV hemolysis
signs of fragmentation
• IV coagulation

• Vasculitis

• Hemangiosarcoma

• Caval syndrome

• Cardiac valvular disease

• Schistocyte
babesia canis
mycoplasma hemofelis
Anaplasma marginale

• Looks like a Howell Jolly body
- Usually seen on more immature RBCs
- on margin of mature RBCs
Heinz body

ingestion of onions, tylenol, red maple leaves

oxidation of sulfhydrily groups on globin chain

denaturation and precipitation of globin chain

heinz body forms and adheres to inside of RBC membrane
What are Heinz bodies?

What causes them?

What is the mechanism?
Aggregated denatured hemoglobin

• Ingestion of onions, Tylenol, maple leaves, acetaminophen, propylene glycol, skunk musk, Zn toxicity, idiopathic
• Cats have more sulfhydryl groups, and their spleen is less able to get rid of Heinz bodies, can be seen in normal cats
o Seen w/ hyperthyroidism, diabetes mellitus and LSA

• Eat bad thing -> oxidation of sulfhydryl groups on globin chain-> denaturation and precipitation of globin chain-> heinz body forms and adheres to inside of RBC membrane
6 causes of Heinz bodies
Onions and garlic


Propylene glycol

Skunk musk

Zinc toxicity

6 causes of Heinz bodies
Onions and garlic


Propylene glycol

Skunk musk

Zinc toxicity