Fall 2011 - Clin Path - Test 1 - Quiz 1

Front 1

Explain why RBCs rely on glycolysis for energy production

Back 1

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

Front 2

Define hematopoiesis

Back 2

The formation, proliferation, and maturation of blood cells

Front 3

define leukopoiesis

Back 3

The formation, proliferation, and maturation of leukocytes

Includes granulopoiesis, lymphopoiesis, and myelopoiesis

Front 4

define erythropoiesis

Back 4

The formation, proliferation, and maturation of erythrocytes

Front 5

define myelopoiesis

Back 5

The formation, proliferation, and maturation of nonlymphoid leukocytes

Front 6

Platelet production consists of ________ & ______

Back 6

megakaryopoiesis and thrombopoiesis

Front 7

The formation of platelets from megakaryocytes

Back 7

thrombopoiesis

Front 8

Erythron

Back 8

All erythroid cells in an animal (includes precursors)

Front 9

Leukon

Back 9

All leukocytes in an animal (includes precursors)

Front 10

Thrombon

Back 10

All megakaryocytes and platelets in an animal (includes precursors)

Front 11

Hematopoiesis occurs primarily where


Where else can it occur?

Back 11

In the bone marrow


Spleen, liver, kidney, and lymph nodes

Front 12

______ refers to hematopoiesis that occurs in the spleen (or liver)

Back 12

Extramedullary hematopoiesis

Front 13

_______ are self-renewing cells that are common ancestors of all blood cells

Back 13

hematopoietic stem cells

Front 14

The main hematopoietic lineages in the bone marrow are _______

Back 14

Erythroid, myeloid (nonlymphoid leukocytes, mainly neutrophils), and megakaryocytic

Front 15

Where to T lymphocytes derive from

Back 15

Bone marrow stem cells

Front 16

The hematopoietic system is under _____ control

Back 16

local and systemic

Front 17

The marrow cavity is interlaced with venous sinuses composed of a luminal layer of ____ and an abluminal layer of _______


Where does hematopoiesis take place

Back 17

Luminal layer of specialized endothelial cells

Abluminal layer of specialized fibroblasts known as adventitial reticular cells

Between these venous sinuses

Front 18

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

Back 18

Sinusoidal endothelial cells along with their basement membrane

Front 19

______ forms a scaffolding which supports the hematopoietic cells of the bone marrow

Back 19

adventitial reticular cells

Front 20

_____ are a major component of marrow tissue with increases in amount with age

Back 20

fat cells

Front 21

_______ provides structural support to the marrow via remodeling bone within the marrow space & likely contribute to regulation of hematopoietic stem cell proliferation and trafficking

Back 21

Osteoblasts, osteoclasts, and elongated flat cells

Front 22

_____ provide structural & biochemical support to the marrow to support the hematopoietic process

Back 22

Specialized stromal cells (presumably of fibroblast origin)

Front 23

What are the different stimuli that drive proliferation and maturation of the 3 main cell lineages of hematopoiesis

Back 23

Erythropoiesis
-Hypoxia detected by JG cells which produced EPO

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

Thrombopoiesis/ Megakaryopoiesis
-Thrombocytopenia results in increased plasma thrombopoietin levels

Front 24

hypoxia has what effect on hematopoiesis

Back 24

increases erythropoiesis

JG cells produce EPO

Front 25

IL-6 has what effect on hematopoiesis

Back 25

increases granulopoiesis

Front 26

increased plasma thrombopoietin levels has what effect on hematpoiesis

Back 26

increases thrombopoiesis

Front 27

Hematopoiesis is subject to ______ kinetics (in health)

Back 27

steady state kinetics

Front 28

Give the general maturation times and life spans for neutrophils, platelets, RBC, lymphocytes (days/ weeks/ months/ years)

Back 28

Neutrophils
-Maturation: 7 days
-Survival: hrs

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

RBC
-Maturation: 5 days
-Survival: 100 days

Lymphocytes
-Maturation: 7 days
-Survival: years (for some)

Front 29

If a virus wiped out all of the early precursors, what cell lineage be depressed first on blood work

Back 29

Neutrophils
b/c survival is only hours

Front 30

What is the dominant regulator of erythropoiesis

What is it and what effect does it have

Back 30

Erythropoietin

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

Front 31

What effect does hypoxia have on EPO production

How?

What happens under normal conditions?

Back 31

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

Front 32

Granulopoiesis is regulated by what

Where does it come from

Normal maturation time

Back 32

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.

Front 33

How are platelets formed

Back 33

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

Front 34

_______ is the primary regulator of neutropoiesis

Back 34

granulocyte colony stimulating factor

Front 35

define plasma

how do you collect it

Back 35

the fluid (acellular) component of circulating blood

it is harvested after centrifugation of an anticoagulated blood sample

Front 36

define serum

Back 36

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

Front 37

how are plasma and serum different

Back 37

plasma is collected from anticoagulated blood
- contains fibrinogen


serum is from coagulated blood
- lacks fibrinogen

Front 38

_____ is the major protein which differentiates plasma from serum

Back 38

fibrinogen
- present in plasma (anticoagulated)
- not present in serum (coagulated)

Front 39

what are the fxns of plasma proteins

Back 39

enzymes
- plasminogen

antibodies
- IgM, IgG, IgA

inflamatory mediators
- complement
- C reactive protein

coagulation factors
- thrombin
- factor x

hormones
- glucagon
- insulin
- growth hormone

transport substances
- transferrin
- lipoproteins

nutritive
- amino acids

Front 40

______ is the principal force opposing the exit of fluid from the vascular system

Back 40

colloidal osmotic pressure

Front 41

decreased ______ results in edema

Back 41

colloidal oncotic pressure

Front 42

decreased _____ causes ascites

Back 42

colloidal osmotic pressure

Front 43

decreased ____ causes hydrothorax

Back 43

colloidal osmotic pressure

Front 44

decreased _____ causes increased total body water

Back 44

colloidal osmotic pressure

Front 45

_____ is the contribution to effective osmolality from macromolecules (mainly albumin)

Back 45

colloidal osmotic pressure

Front 46

changes in _____ cause sshifts between ECF and ICF

Back 46

extracellular (serum) osmolality

Front 47

extracellular (serum) osmolality

Back 47

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

Front 48

osmolality vs COP

which has proteins as a major contributor

which has electrolytes as a major contributor

Back 48

COP


extracellular (serum) osmolality

Front 49

how do you determine serum osmolality

Back 49

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

Front 50

rapid changes in _____ can cause cellular edema

Back 50

extracellular (serum) osmolality

Front 51

rapid changes in ______ can cause hemolysis

Back 51

extracellular (serum) osmolality

Front 52

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

Back 52

1. hepatocytes
2. lymphoid tissue
3. hepatocytes
4. hepatocytes
5. endothelial cells
6. lymphoid tissue

Front 53

what are acute phase proteins?

where are they made?

Back 53

alpha and beta globulins

made by hepatocytes

Front 54

How do you measure total protein

Back 54

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)


refractometry
- 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

Front 55

how do you measure albumin (g/dl)

Back 55

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

Front 56

how do you measure globulin (g/dl)

Back 56

calculated
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

Front 57

how do measure for failure of passive transfer in calves/ foals

Back 57

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

Front 58

how do you measure fibrinogen (mg/dl)

Back 58

heat precipitation method
- crude test
- usually done in conjuction with large animal CBC to screen for Hyperfibrinogenemia
- NOT sensitive enough to detect hypofibrinogenemia

Front 59

______is the darkest band (and therefore the highest peak) for mammals on protein electrophoresis

Back 59

albumin

Front 60

what test is used to check for hypofibrinogenemia?

hyperfibrinogenemia?

Back 60

hypo
- (modified) thrombin time

hyper
- heat precipitation test

Front 61

when would you want to use protein electrophoresis

Back 61

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

Front 62

HYPERPROTEINEMIA
what do you expect with each of the following protein abnormalities

1. Relative (dehydration)

2. Hyperalbuminemia

3. Hyperglobulinemia

4. Inflammation

5. Neoplasia

6. Hyperfibrinogenemia

Back 62

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

Front 63

decribe the positive acute phase inflammatory reaction

Back 63

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)

Front 64

describe the negative acute phase inflammatory rxn

Back 64

hepatic synthesis of neg acute phase proteins is decreased w/in days to weeks of inflammatory stimulus
~ albumin
~ transferrin

Front 65

what do you expect to see in a protein electrophoresis if a plasma cell becomes neoplastic (myeloma)

Back 65

monoclonal gammopathy
- tall, narrow spike in beta or gamma globulin region

need immunoelectrophoresis to identify Ig glass involved and confirm monoglonal gammopathy

Front 66

what are the differentials for a monoclonal gammopathy

Back 66

neoplasia of plasma cell (myeloma)

canine ehrlichiosis

canine leishmaniasis

FIP

(the last 3 are not true monoclonal gammopathy, they are restricted polyclonal or oligoclonal)

Front 67

HYPOPROTEINEMIA
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

Back 67

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)

Front 68

in what situation would you expect albumin loss but no globuin loss

Back 68

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

Front 69

What do you expect protein values too look like with dehydration?

Back 69

TP - increased
Alb - increased
Glob - increased

Front 70

What would you expect the protein values to look like with chronic inflammation

Back 70

TP - increased
Alb - normal to decreased
Glob - increased

Front 71

What would you expect the protein values to look like with glomerular dz

Back 71

TP decreased
Alb - decreased
Glob - normal

Front 72

What would you expect protein values to look liek with failure of passive transfer

Back 72

TP - decreased
Alb - normal
Glob - decreased

Front 73

What would you expect protein values to look like with protein losing eneteropathy

Back 73

TP - decreased
Alb - decreased
Glob - decreased

Front 74

What would you expect protein values to look like with hemorrhage

Back 74

TP - decreased
Alb - decreased
Glob - decreased

Front 75

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)

Back 75

TP - decreased
Alb - decreased
Glob - decreased

b/c severe malabsorption

Front 76

A heat precipitation test is used to detect what

Back 76

hyperfibrinogenemia

(hyopfibrinogenemia is measured with a modified thrombin time)

Front 77

3 classifications of anemia *and what they are characterized by (ie reticulocytosis or not)*

Back 77

nonregenerative
- no reticulocytosis

preregenerative
- impending reticulocytosis

regenerative
- 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)

Front 78

how do mature RBC differ from reticulocytes

Back 78

mature
- smaller
- normal Hgb
- no RNA
- pink staining (normochromasia)
- neg NMB staining


reticulocyte
- larger
- lower Hgb
- contains RNA
- purple staining (polychromasia)
- pos NMB staining

Front 79

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

Back 79

1. a. yes (low #s)
b. no
c. no


2. a. yes
b. yes
c. no (damn you Mr. Ed)

Front 80

describe the anemia of inflammation

Back 80

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

Front 81

most regenerative anemias are _____ (Macro/normo/microcytic), ____ (macro/normo/ microchromic)

non-regenerative anemias?

Back 81

regenerative
- most are normocytic normochromic

non-regenerative
- most are normocytic normochromic
- can be macrocytic hypochromic

Front 82

describe hepcidin and its effect on inflammatory anemia

Back 82

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

Front 83

what is hepcidin's effect in a nutshell

Back 83

inhibits intestinal absorption fo iron and release of iorn stored in macrophages

Front 84

when do you see true iron deficiency?

what does it look like _____cytic, _____chromic anemia

Back 84

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

Front 85

is blood loss normall regenerative or nonregenerative

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

Back 85

normally regenerative

with the exception of iron deficiency b/c it can be regen or nonregen

Front 86

why do you see anemia with CRF

Back 86

decreased erythropoiesis

secondary to decreased EPO production by JG cells

Front 87

how does thyroid fxn affect anemia?

Back 87

hypothyroidism
- decreased erythropoiesis
- decreased EPO production
- decreased EPO responsiveness
- someone in our class is screwed, and it's not me :)

hyperthyroidism
- 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)

Front 88

increased heinz bodies in cats are associated with

Back 88

hyperthyroidism

diabetes mellitus

lymphoma

Front 89

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

Back 89

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

Front 90

how does chronic liver dz affect erythropoiesis

Back 90

non-regenerative anemai
- inflammation
- abnormal metabolism of AAs/ Proteins/ Lipids
- defective Fe handling

Portosystemic shunts
- often microcytic (mx not understood)

Front 91

in what infectious diseases do you expect to see thrombocytopenia with anemia

Back 91

FeLV

EIAV (equine anemia virus)

infect erythropoietic cells
- direct suppression of early stage erythropoietic cells
- inflammation
- immune mediated hemolysis

Front 92

FeLV (in relation to hemopoiesis)

Back 92

causes wide spectrum of hematologic abnormalities

often macrocytic in the absence of reticulocytosis

subgroup C (uncommon) assoc with erythroid aplasia

Front 93

Cat CBC shows macrocytosis (without normal pattern of macrocytic hyperchromic regenerative anemia). What is the dx

Back 93

FeLV

Front 94

toxic injury to marrow shows what on CBC

give examples that could cause this

Back 94

nonregenerative anemia

pancytopenia
- generalized suppression of hematopoiesis

chemical agents
- chemo
- hyperestrogenism
- bracken fern toxicity

irradiation

Front 95

myelophthisis causes what kind of anemia

Back 95

non-regenerative

fibrosis

neoplasia (hematopoietic or metastatic)

osteopetrosis

replacement of hematopoietic tissue in marrow with other tissue (usually fibrous CT)

Front 96

nonregenerative IMHA

Back 96

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

Front 97

name some (rare) causes of anemia

including nutritional (not iron) and congenital

Back 97

nutritional deficiencies
- copper (disrupts iron metabolism)
- folate or cobalamin (B12) *nutritional or inherited*

congenital dyserythropoiesis
- Engl Springer Spaniels
- Polled Herefords

Front 98

anemia in animals with neoplasia is most often ____ (regen/ nonregen)

why

Back 98

non-regenerative

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)

Front 99

Back 99

Front 100

Back 100

Front 101

Back 101

Front 102

describe erythrocytosis

what effect does it have on MCH/ MCHC

Back 102

Increase in total number of RBC

not increase in Hgb so no increase in MCH/ MCHC

Front 103

how will lipemia affect your CBC

Back 103

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

Front 104

define erythrocytosis

Back 104

increased circulating RBC mass

Front 105

what does the erythrogram show increases in for erythrocytosis

Back 105

RBC (#/ul)

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

Hgb (g/dL)

Front 106

what are some non-pathologic causes of absolute erythrocytosis

Back 106

breed variations

physiologic

doping

idopathic (mild)

Front 107

what is relative erythrocytosis

Back 107

not really more RBC, just looks like it

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

redistribution of RBC
- splenic contraction (esp horses)

Front 108

what are the causes of primary erythrocytosis

Back 108

primary = non EPO dependent

polycythemia vera
- type of hematopoietic stem cell neoplasia

mutations affecting EPO receptor or transcriptional regulation of EPO

Front 109

what are causes of secondary appropriate erythrocytosis

Back 109

right to left shunts (hypoxia)
- PFO
- PDA

pulmonary dz (hypoxia)
- due to less oxygen exchange

hyperthyroidism
- increased demand for O2
- direct effect of thyroid hormone on erythropoiesis?
- assoc with anemia?

Front 110

appropriate vs inappropriated erythrocytosis

Back 110

appropriated
- 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

inappropriate
- not in response to anemia/ hypoxia

Front 111

syndrome

malignant neoplasia

benign neoplasia

Back 111

syndrome
- collection of symptoms

malignant neoplasia
- characterized by spread (metastasis)/ invasion

benign neoplasia
- no metastasis or invasion

Front 112

secondary inappropriate erythrocytosis causes

Back 112

Renal lesions secreting EPO
- neoplasia
- cysts

extra-renal neoplasia secreting EPO

Front 113

what are some non-pathologic causes of erythrocytosis (4)

Back 113

breed variations

physiologic

doping

idiopathic

Front 114

how do you diagnose the different types of erythrocytosis

Back 114

relative
- 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]

Front 115

hyperviscosity syndrome

Back 115

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)

Front 116

causes of regenerative anemia

Back 116

blood loss

hemolysis
- immune mediated
- fragmentation
- infectious
- metabolic
- heinz body

Front 117

what is the term for increased MCV?

decreased MCHC?

Back 117

increased MCV
- macrocytosis

decreased MCHC
- hypochromasia

Front 118

________ is almost always artifact (macrocytosis/ microcytosis/ hyperchromasia/ hypochromasia

Back 118

hyperchromasia

Front 119

most regenerative anemias are ___cytic, ____chromic

Back 119

normocytic normochromic

Front 120

what does an iron deficient anemia look like

Back 120

microcytic, microchromic

microcytic, normochromic

Front 121

agglutination has what effect on MCV

Back 121

false increase

Front 122

what 2 entities represent the same cell stained 2 different ways (Romanowsky & NMB) which represent regeneration

Back 122

Romanowsky Stain
- polychromatophilic macrocyte

NMB
- Reticulocyte

Front 123

______ is a visual suggestion that we have a regenerative anemia

Back 123

polychromasia

Front 124

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?

Back 124

Reticulocyte


look for polychromasia

Front 125

Back 125

anisocytosis

variation in cell size

Front 126

suggestions of regeneration

Back 126

polychromasia/ reticulocytosis

anisocytosis
- 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

Front 127

If you see a dog with nucleated RBC and basophilic stippling, what is your dx

Back 127

lead toxicity (not regenerative anemia)

Front 128

If you see a cow with nucleated RBC and basophilic stippling, what is your dx

Back 128

regenerative anemia

Front 129

When is rubricytosis appropriate?

inapproprite

Back 129

rubricytosis = nucleated RBC present

appropriate
- regeneration
- in presence of reticulocytes


inappropriate
- marrow damage (necrosis/ inflammation/ endotoxemia/ heat stroke/ neoplasia)
- extramedullary hematopoiesis
- splenic contraction or splenectomy
- lead poisoning with basophilic stippling

Front 130

____ is THE BEST method for determining marrow response to anemia

what are the #'s for reference

how long does it take

Back 130

Reticulocyte concentration/ count

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

takes 2-3 days after initiation of anemia

Front 131

Back 131

nucleated RBC (metarubricyte)

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

Front 132

Back 132

Spherocyte

Must
- Look smaller
- No central pallor
- Be round

Halfway eaten cells

Front 133

Back 133

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

Front 134

Back 134

Acanthocytes

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)

Front 135

Echinocyte/crenation vs. Acanthocyte

Back 135

Echinocytes/ crenation
- Spikey but not clubbed
- Rattle snake venom

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

Front 136

Back 136

Heinz Body

Aggregated denatured Hb

Blue on NMB

Clear on romanowsky stain

Often protruding from cell

Dogs
- Never normal
- Due to oxidative damage

Cats
- See more often

Front 137

evidence of hemolysis consists of

Back 137

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

hemoglobinuria

erythrocyte chagned associated with causes of hemolysis

Front 138

normal RBC breakdown/ bilirubin metabolism

Back 138

In liver it is broken down into

Protein

Hemoglobin
- 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

Front 139

Hemolytic anemia findings

Back 139

poikilocytosis or cell inclusions

neutrophilic leukocytosis

reticulocytosis

splenomegaly

Front 140

what does the CBC of a IMHA case look like

Back 140

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 +/-

Front 141

what does the leukogram of a IMHA case look like

Back 141

WBC up

Segs up

Bands normal

lymphs down

monos up

Front 142

What is the horse’s HCT and TP minutes after the deep laceration is made? 12 hours? 5 days? 2 weeks?

Back 142

Front 143

evidence of hemolysis consists of

Back 143

pre-hepatic hyperbilirubinemia and bilirubinuria

hemolyzed plasma

hemoglobinuria

erythrocyte changes associated with causes of hemolysis

Front 144

intravascular vs extravascular hemolysis

Back 144

IV
- Hgb - Released into plasma (red plasma in HCT tube)
- Freely filtered to urine


EV
- pre-hepatic hyperbilirubinemia and bilirubinruia
- overflow of unconjugated bilirubin from macrophages (conjugated in K9 kidney)
- overflow of conjugated bilirubin from liver
results in bilirubinuria

Front 145

What kind of bilirubin can be excreted in urine

Back 145

conjugated bilirubin

Front 146

prehepatic hyperbilirunemia causes

Back 146

overflow of conjugated bilirubin from liver

overflow of unconjugated bilirubin from the macrophage

Front 147

what do you see with IMHA

Back 147

Poikilocytosis or cell inclusions

Neutrophilic leukocytosis

Reticulocytosis

Splenomegaly

Inflammatory leukogram +/-

Spherocytosis +/-

Evans syndrome +/-

Agglutination +/-

Coombs’ Test positive +/-

Front 148

signs of hemolysis (IV vs EV)

how does normal RBC breakdown/ bilirubin metabolism occur

Back 148

IV
- Hemoglobin released into plasma -> red plasma in HCT tube -> freely filtered into urine

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


Normal
• 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

Front 149

causes of IMHA

Back 149

Idiopathic or autoimmune

Drug induced

Isoimmune (NI)

Blood transfusion

Front 150

Back 150

agglutination

held together by antibodies

Front 151

Back 151

rouleaux

formation due to reduction in membrane charge

Front 152

IMHA CBC & Leukogram

Back 152

CBC
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

Front 153

IMHA blood smear

Back 153

spherocytosis +/-, agglutination +/-

Hemolysis, icterus, spherocytes, clumping of RBCs


Clumping
• 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”)

Front 154

Signs of IMHA

Back 154

o Fever
o Anorexia
o Weakness
o Prolonged CRT
o MM pale and icteric

Front 155

Mechanism of IMHA

Back 155

Macrophages get a little premature w/hemolysis, release inflammatory cytokines

 Leads to leukocytosis and presence of spherocytes

 Activates C’, leads to IV hemolysis

Front 156

signs of fragmentation

Back 156

• IV coagulation

• Vasculitis

• Hemangiosarcoma

• Caval syndrome

• Cardiac valvular disease

• Schistocyte

Front 157

Back 157

babesia canis

Front 158

Back 158

mycoplasma hemofelis

Front 159

Back 159

Anaplasma marginale

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

Front 160

Back 160

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

Front 161

What are Heinz bodies?

What causes them?

What is the mechanism?

Back 161

Aggregated denatured hemoglobin


Causes
• 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


Mechanism
• 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

Front 162

6 causes of Heinz bodies

Back 162

Onions and garlic

Acetaminophen

Propylene glycol

Skunk musk

Zinc toxicity

Idiopathic

Front 163

6 causes of Heinz bodies

Back 163

Onions and garlic

Acetaminophen

Propylene glycol

Skunk musk

Zinc toxicity

Idiopathic