Leukocytes Flashcards

1
Q

What makes up a complete blood count?

A

Leukogram
Erythrogram
Thrombogram

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2
Q

What is a leukogram?

A

Evaluation of leukocytes

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3
Q

What is an ertythrogram?

A

Evaluation of erythrocytes

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4
Q

What is a thrombogram?

A

Evaluation of platelets

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5
Q

What does it mean if the results of a CBC are within the reference interval?

A

Minimal effect of disease

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6
Q

What does it meant if the CBC shows increased cell concentration?

A

Increased production
Shift from SP or other non-circulating pool to CP
Increased blood life span

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7
Q

What does it mean if the CBC shows decreased cell concentration (cytopenia)?

A

Decreased production
CP to non-circulating pool
Decreased life span

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8
Q

What should the CBC blood sample be like?

A

K2EDTA, K3EDTA (purple top)
No clots or platelet clumps
Several hours RT or 24 hours in refrigerator at 4C

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9
Q

Describe microscopic evaluation

A

Always a part of CBC

Blood film with 4 parts: blood drop site, thick area, monolayer, feathered edge

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10
Q

What is the most important art of blood film?

A

Monolayer

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11
Q

Describe the monolayer?

A

Erythrocytes occasionally touch each other and leukocytes’ nuclear and cytoplasmic features are visible

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12
Q

What is stained with a romanowsky stain?

A
Acidic structures (basophilic/blue): DNA and RNA
Alkaline structures (eosiniophilic/red): hemoglobin and eosinophil granules
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13
Q

What are the descriptive terms used with a romanowsky stain?

A

Neutrophilic
Eosinophilic
Basophilic
Azurophilic

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14
Q

What are ways to determine leukocyte concentration?

A

Impedance and flow cytometer counters

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15
Q

Describe impedance counters

A

A current that passes from cathode to anode. Cells disrupt the current when it passes through there and once it happens you can count how many cells pass and measure size

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16
Q

Describe flow cytometer counters

A

Cells passes through a laser which heats the cell. It will heat the things inside the cells and scatter the light. This can tell a cell apart by the presence of light and how it changes the trajectory. It can also tell how much of something is inside a cell

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17
Q

Do we use relative or absolute changes?

A

We use absolute. Relative changes may not reflect true changes

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18
Q

Where are most leukocytes produced?

A

In the bone marrow

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19
Q

What will you see if the bone marrow isn’t producing a lot of cells?

A

More adipose cells

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20
Q

What are the leukocytes in tissues?

A

Granulocytes (netrophils, eosinophils, basophils)
Lymphocytes
Monocytes (histiocytes or macrophages)
Mast cells

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21
Q

What is the function of granulocytes?

A

Defense and die

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22
Q

What is the function of lymphocytes?

A

Blastogenesis, return to blood, or die

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23
Q

What is the function of monocytes?

A

Defense and die

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24
Q

What is the function of mast cells?

A

Defense and die

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25
Q

What is blastogenesis?

A

Transformation of small lymphocytes of peripheral blood into cells capable of undergoing mitosis

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26
Q

Describe the process of neutrophil maturation

A
Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Band
Neutrophil
Hypersegmented
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27
Q

What are the leukocytes pools?

A
Production pool (ProNP)
Maturation pool (MatNP)
Storage pool (SNP)
Circulating pool (CNP)
Marginating pool (MNP)
Tissue
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28
Q

What pools are in the bone marrow?

A

ProNP
MatNP
SNP

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29
Q

What pools are in the blood?

A

CNP (free flowing)

MNP (adhered)

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30
Q

What pool are you taking from when you get a blood sample?

A

Circulating

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31
Q

What regulates neutrophil production?

A
IL-1
IL-3
IL-6
GM-CSF
G-CSF
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32
Q

What chemoattractants cause the release of neutrophils?

A

C5a
IL-8
LTB4
PAF

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33
Q

What cytokines cause the release of neutrophils?

A
IL-1
IL-6
TNFα
TNFβ
G-CSF
GM-CSF
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34
Q

What is the half life on neutrophils in the blood?

A

5-10 hours

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35
Q

What is the ratio of CNP:MNP in the blood?

A

1: 1 for most mammals
3: 1 for cats

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36
Q

What contributes to blood neutrophil concentration?

A

Production
Release
CNP:MNP
Migration to tissue

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37
Q

What causes neutrophils to migrate to tissues?

A

C5a
IL-8
LTB4
PAF

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38
Q

What is a left shift in neutrophil concentration?

A

Increase of non-segmented neutrophils in the blood

Above the reference interval

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39
Q

What is a left shift in neutrophil concentration the hallmark of?

A

Acute inflammation

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40
Q

What are common causes of a left shift?

A

Steroids and endotoxin

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41
Q

Describe the left shift severity classification

A

Bands: mild, 1000/μL
Bands and metamyelocytes: moderate, 1000-10,000/μL
Bands, metamyelocytes, and myelocytes: marked, more than 10,000/μL

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42
Q

What qualifies as a degenerative left shift?

A

Non-segmented neutrophils greater than segmented neutrophils

Segmented neutrophils is less than the reference interval

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43
Q

What qualifies as a regenerative left shift?

A

Segmented neutrophils are greater than the reference interval and segmented neutrophil is greater than non-segmented
Segmented within the reference interval is not classified

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44
Q

Which has a better prognosis, degenerative or regenerative left shift?

A

Regenerative

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45
Q

What is the clinical relevance of a left shift?

A

Prognostic tool
Regenerative: adequate response to the inflammatory process
Degenerative: inadequate response

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46
Q

What is a right shift in the neutrophil concentration?

A

Increased numbers of hypersegmented neutrophils (5 or more segmentations)

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47
Q

What is the most common cause of a right shift?

A

Glucocorticoid hormones (endogenous and exogenous)

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48
Q

What indicates neutrophilia/acute inflammation?

A

Inflammatory mediators
Increase CNP (may contain bands)
Release of SNP occurs in hours
Release of MatNP occurs after depletion of SNP
Increased production from stem cells, 5 days

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49
Q

Why are mediators necessary in acute inflammation?

A

To increase the release of neutrophils

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50
Q

What does the magnitude of neutrophilia depend on?

A

Species

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51
Q

What is the leukemoid response?

A

Occurs with neutrophilia/acute inflammation

Looks like leukemia but is proven not to be

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52
Q

What is unique about bovine and the SNP?

A

It is small, so you need to increase production

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53
Q

Describe neutrophilia/chronic inflammation

A

Inflammation after at least a week
Replenishment of SNP: release of segs, not bands
Less severe neutrophilia
With persistent intense stimulus, acute inflammatory response continues

54
Q

Describe neutrophilia due to steroid (stress)

A

Endogenous or exogenous glucocorticoids
Shift from MNP to CNP
Doubles (canine, equine, bovine), greater in felines
Decreased emigration to tissues, increased circulating life span
Increased release from BM: mostly mature, but also bands
Most frequently seen in dogs (neutrophilia, monocytosis, lymphopenia, and eosinopenia)
Left shift (less than 1000/μL), right shift, or no shift

55
Q

Describe neutrophilia due to physiologic shift

A
Catecholamines
Shift from MNP to CNP
Doubles for dogs, horses, and cattle, triplicate or quadruplicate for feline
Frequently in healthy animals
Back to "normal" in 60 minutes
May increase lymphocytes numbers too
56
Q

Describe neutrophilia due to chronic myeloid leukemia

A

Clonoal proliferation
Mature (segmented) neutrophils
Difficult to differentiate from extreme neutrophilia

57
Q

Describe neutrophilia that is paraneoplastic

A

Neoplastic cells can produce G-CSF or a similar substance

Adenomatous polyp, renal tubular carcinoma, metastatic fibrosarcoma

58
Q

What are some other causes of neutrophilia?

A

Leukocyte adhesion deficiency from a lack of CD18
G-CSF administration
Estrogen toxicosis

59
Q

What is the main cause of neutropenia?

A

Overwhelming inflammation

60
Q

Describe neutropenia due to inflammation

A

Migration exceeds release
Mediators also cause increased production but it will take at least 2 days to see blood changes
SNP is released first, then MatNP; if migration is too severe left shift then it may not be present (bands migrating fast too)
Common in cattle because the have a small SNP

61
Q

Describe neutropenia due to endotoxemia

A

Margination of neutrophils
Duration is 1 to 3 hours
Stimulate release from BM in 8 to 12 hours
Stimulate production: 3-5 days

62
Q

Describe neutropenia due to immune-mediated peripheral destruction

A

Ab binds to neutrophils
Destruction by mononuclear phagocyte system
May be responsive to glucocorticoid treatment
May see granulocytic hyperplasia in BM

63
Q

Describe neutropenia due to peripheral destruction from hemophagocytic syndrome

A

Phagocyte hyperplasia
May see other cytopenias
In people, it is secondary to infections and neoplastic cells

64
Q

What is the size of small lymphocytes compared to erythrocytes?

A

1 to 1.5 erythrocytes

65
Q

What is the size of medium lymphocytes compared to erythrocytes?

A

1.5 to 2 erythrocytes

66
Q

What is the size of large lymphocytes compared to erythrocytes?

A

More than 2 erythrocytes

67
Q

What are the lymphocytes in the blood?

A

Most are T lymphocytes

CLP and MLP

68
Q

What happens to lymphocytes in lymph nodes?

A

Enter cortices via specialized postcapillary venules
Exit via efferent lymphatic vessels
25% enter lymph nodes each day

69
Q

What happens to lymphocytes in the tissue?

A

Blastogenesis, recirculate, or die

Migration from vessels to tissue similar to neutrophils

70
Q

What is the blood concentration of lymphocytes?

A

Production (stem cell or blastogenesis)
CLP and MLP
Life span is hours to years

71
Q

Describe lymphocytosis due to chronic inflammation

A
Chronic antigenic or cytokine stimulus
Reactive lymphocytes may be present
Enlarged lymph nodes or lymphoid organs
Mild to moderate
Neutrophilia, monocytosis
72
Q

Describe lymphocytosis due to physiologuc shift

A
Catecholamines
MLP to CLP
2 x URL
Minutes to hours
No morphologic change
May cause large granular lymphocytes to increase
73
Q

Describe lymphocytosis due to lymphoproliferative disease

A

Neoplastic proliferation
Lymph nodes, BM, other tissues
BLV and FeLV
Leukemia may be leukemic manifestation of lymphoma
Leukemia: marked lymphocytosis with cells displaying immature features

74
Q

Describe lymphocytosis dues to hypoadrenocorticism

A

Lack of glucocorticoids
Dogs: neutropenia with lymphocytosis and azotemia
May also see high normal to mild eosiniophilia

75
Q

Describe lymphocytosis in young animals

A

Cattle: increases until 1 year old and then gradually decreases
Up to 2 URL

76
Q

Describe lymphopenia due to acute inflammation

A

Change in lymphocyte kinetic decreasing CLP

It my be caused by stress

77
Q

Describe lymphopenia due to steroids/stress

A

Change in lymphocyte kinetics decreasing CLP
Endogenous and exogenous glucocorticoids
Immediate shift from CLP to other pools. May be entrapped in lymph nodes or BM
Later lymphotoxic effects leading to lymphoid hypoplasia

78
Q

What is the most common cause of lymphopenia?

A

Steroids/stress

79
Q

Describe lymphopenia due to depletion

A

Loss of lymphocytes due to incomplete circulation

Repeated chylothoracic fluid removal in cats

80
Q

Describe lymphopenia die to lymphoid hypoplasia or aplasia

A

Congenital or acquired
Decrease lymphocyte production
Selective T lymphocyte hypoplasia or aplasia will cause more severe lymphopenia than selective B lymphocyte hypoplasia or aplasia

81
Q

Describe lymohopenia due to lymphoma

A

Common in animals with lymphoma

Decrease production or altered kinetics

82
Q

What are monocytes produced from?

A

Stem cells: CFU-GM (granulocytes)

83
Q

What pools are avaiable in the vessel for monocytes?

A

CMP and MMP

84
Q

What happens once monocytes get to the tissue?

A

They form the mononuclear phagocyte system

85
Q

What makes up the mononuclear phagocyte system?

A

Macrophages
Microglial cells
Dendritic cells

86
Q

Describe monocytosis due to inflammation

A

Acute and chronic inflammation

Cytokine stimulation: production and release

87
Q

Describe monocytosis due to steroids/stress

A

Common in dogs and cats, minimal in horses and cattle

Shift from MMP to CMP

88
Q

Describe monocytosis due to neoplastic cells

A

Monocytic leukemia
Marked monocytosis
Normal and abnormal monocytes
Uncommon when compared to granulocytic and lymphoid leukemias

89
Q

Describe monocytosis that is secondary to immune-mediated neutropenia

A

Monocytes and neutrophils share common progenitor

May increase monocytopoiesis when stimulating neutropoiesis

90
Q

Describe monocytosis due to cyclic hematopoiesis

A

Mild during neutropenic cycles

Herald increase neutrophil concentration

91
Q

Describe monocytosis due to G-CSF treatment

A

Increase production of neutrophils and monocytes

92
Q

Why is monocytopenia difficult to document?

A

The lower reference limit is already very low for monocyte concentration, but it is not considered a diagnostic problem

93
Q

What causes differentiation with eosinophils?

A

IL-5

GM-CSF

94
Q

What are the pools for eosinophils in the blood?

A

CEP and MEP (minutes to hours in the blood)

95
Q

What do eosinophils do in the tissue?

A

Bactericidal properties
Inactivate mast cell mediators
Attack parasite larvae and adult stages

96
Q

What is eosinophilia due to?

A
Anti-inflammatory function
Attraction after mast cells or basophil degranulation
Hypersensitivity
Internal and external parasites
Inflammation in mast cells rich tissues
Occasionally in hypoadrenocorticism
97
Q

Describe eosinophilia due to idiopathic hypereosinophilic syndrome

A

Cats, dogs, horses
Persistent marked eosinophilia without apparent cause
No features suggestive of leukemia
Hypereosinophili: more than 20,000/μL

98
Q

Describe eosinophilia due to paraneoplastic effects

A

Mast cell neoplasms
Other neoplasms that can release IL-5
Dogs: T cell lymphoma, thymoma, mammary carcinoma, oral fibrosarcoma, and rectal adenomatous polyp
Cats: TCC, T cell lymphoma, and alimentary lymphoma
Horses: intestinal lymphomas

99
Q

When should basophilia be considered?

A

When it is persistently above 200 to 300 μL

100
Q

What are causes of basophilia?

A

Allergic, parasitic, and neoplastic states

101
Q

Why is a basopenia hard to documaent?

A

There is already a very low LRL for basophil concentration, but it is not known to be clinically relevant

102
Q

What are toxic neutrophils?

A

Neutrophils with toxic changes

103
Q

What are examples of toxic changes?

A

Foamy cytoplasm
Diffuse cytoplasmic basophilia
Dohle’s bodies
Giant neutrophils

104
Q

What is a foamy cytoplasm?

A

Cytoplasmic clearing due to dispersed organelles

105
Q

What is diffuse cytoplasmic basophilia?

A

Retention of RNA during maturation
Segmented neutrophils should not have this, so when they do, it is considered a toxic change
A normal band will have this

106
Q

What are Dohle’s bodies?

A

Aggregates of rough endoplasmic reticulum

107
Q

What are giant neutrophils?

A

Larger neutrophils due to asynchronous maturation

108
Q

What do toxic changes represent?

A

Maturation defects caused by rapid neutropoiesis

109
Q

What are hypersegmented neutrophils?

A

More than 5 lobes
Typically old neutrophils
Myelodysplastic syndromes involving neutrophilic cell line
Found in Poodle marrow dyscrasia

110
Q

What can reactive lymphocytes be found in?

A

Acute and chronic inflammation

111
Q

What can reactive lymphocytes be difficult to differentaite from?

A

Atypical (neoplastic) lymphocytes

112
Q

Describe monocytes that have features of macrophages

A

Abdundant gray cytoplasm
With or without vacuolation
Seen in systemic infections (histoplasmosis, ehrlichiosis, babesiosis, or leishimaiasis)

113
Q

Describe sideroleukocytes

A

Neutrophil or monocyte containing hemosiderin

Rare, but can be seen with hemolytic anemias and after transfusions

114
Q

Describe erythrophage

A
Neutrophil or macrophages with phagocytized erythrocyte
Occasionally seen with IMHA
Idiopathic immune-mediated anemia dogs
Equine infectious anemia
Neonatal isoerytholysis
115
Q

Describe lupus erythematosus (LE) cells

A

Neutrophil that phagocytized nuclear antigen-antibody complexes
Pink to palke basophilic inclusion of variable sizes

116
Q

Describe bacteria not from the family Anaplasmacetae in leukocytes

A

Rare in patients with bacteremia

Bacteria in blood; can be true bacteremia, can be contamination of the sample

117
Q

Describe bacteria from the family Anaplasmacetae in leukocytes

A

Can invade and multiply in blood leukocytes
Monocytic ones tend to be more species specific
Leukocytic ones are less specific

118
Q

Describe canine distemper inclusions in leukocytes

A

Monomorphic or polymorphic
Red to purplish red or pale blue
Neutrophils, monocytes, lymphocytes, and erythrocytes

119
Q

Describe Hepatozoon americanum in leukocytes

A

Gametocytes infect neutrophils and monocytes

120
Q

Describe Hepatozoon canis

A

Gametocytes infect neutrophils and monocytes
Found in Europe, Asia, Africa, and South America
Lack obvious clinical signs

121
Q

Describe Histoplasma capsulatum in leukocytes

A

Single or multiple in the cytoplasm f neutrophils, monocytes, or eosinophils
Yeasat phase
2 to 4 μm
Eccentric basophilic region with nuclear material

122
Q

Describe Leishmania in leukocytes

A

Kinetoplastid protozoan found primarily in the Mediterranean, central and South American countries
Found in Ohio, Oklahoma, and SE US
Amastigotes found in macrophages

123
Q

Describe Mycobacterium in leukocytes

A

Rarely seen systemic
Can be seen in neutrophils or monocytes
Won’t stain with Wright stain

124
Q

Describe Toxolasma gondii in leukocytes

A

Tachzoites are rarely found in blood neutrophils and monocytes
More common in macrophages of infected organs

125
Q

Describe leukocyte adhesion deficiency (LAD)

A

Irish red and white setters, Holstein cattle
Canine LAD (CLAD) and Bovine LAD (BLAD)
Defects in the integrin CD18
No functional CD11/CD18
Necessary for adherence, migration, and aggreagation

126
Q

Describe CLAD

A

Persistent leukocytosis and granulocytic hyperplasia in the BM
Susceptible to infections
PCR diagnosis

127
Q

Describe BLAD

A

Marked neutrophilia and recurrent infection

PCR diagnosis

128
Q

Describe the Pelger-Huet anomaly

A

Several breeds of dogs, DSH cats, and Arabians
Hyposegmentaion of neutrophils, eosinophils, and basophils
Nuclear chromatin: hyperchomatic or normochromatic
These are not bands because the bands with this anomaly are very condensed rater than more open-faced

129
Q

What are psuedo pelger-huet neutrophils found in?

A

Cows, dogs with severe inflammation, and cats wuth FeLV myeloid leukemia

130
Q

What are psuedo pelger-huet eosinophils found in?

A

Cattle and horses (with neutrophils)

131
Q

Describe nonstaining eosinophil granules (gray eosinophil) of dogs

A

Greyhounds, Golden retrievers, Shetland sheepdog
Poor staining eosinophil granules or just the vacuoles and gray cytoplasm
Modified chemical composition
No pathological significance
Maybe misclassified by counters (ADVIA)