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Leukocytes Flashcards

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1
Q

What is the Proliferative pool of Neutrophils?

A
  • Includes the:
    • Myeloblast
    • Proganulocyte
    • Myelocyte
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2
Q

What is the maturation pool of neutrophils?

A
  • Includes the:
    • Metamyelocyte
    • Band neutrophils (immature neutrophils)
  • Can be released during nonregenerative leukopenia
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3
Q

What are the kinetics of neutrophils during health?

A
  • Transit time in marrow - 7-10days
  • Storage pool - Relatively large supply of mature neutrophils in most species
    • Ruminants have small reserves
  • Blood transit time: ~6-10hr
  • Tissue Lifespan: 24-48hr
  • Destroyed by macrophages in tissue (~90%)
  • Lost in secretions from mucous membranes (~10%)
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4
Q

What is the function of Neutrophils?

A
  • Inflammatory response chemotaxis & phagocytosis - Innate immune response
  • Neutrophils in blood are in transit from site of production to site of function
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5
Q

What is a “left shift”?

A
  • Increased numbers of immature neutrophils in peripheral blood
    • Bands, +/- metamyelocytes & myelocytes
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6
Q

What is a Regenerative Left Shift?

A
  • Expected response
  • Bone marrow is able to keep up
  • Leukocytosis due to neutrophilia
  • [segs] > [non-segs]
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7
Q

What is a Degenerative left shift?

A
  • Bone marrow is NOT keeping up with demand
  • Any time [non-segs] > [segs]
  • Leukopenia due to neutropenia with a left shift where >10% of neutrophils are immatuer
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8
Q

What does a Band Neutrophil look like?

A
  • Generally parallel sides
  • Lacks definitive indentation
  • “Hallmark of acute inflammation”
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9
Q

What do segmented neutrophils look like?

A
  • Definitive indentation in nuclear outline
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10
Q

What are Toxic Changes in Neutrophils?

A
  • Likely the most common morphologic WBC abnormally identified on the blood films
  • Occurs d/t increased stimulus for neutrophil production
    • Storage pool of neutrophils in the bone marrow has been depleted
  • Accelerated neutrophil production results in aberrant granulopoiesis
  • Includes:
    • Diffuse cytoplasmic basophilia
    • Foamy cytoplasm
    • Focal basophilia “Dohle body”
    • Hyalinized nucleus
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11
Q

What are the different mechanisms for Neutrophilia?

A
  • Acute Inflammatory Neutrophilia
  • Chronic Inflammatory Neutrophilia
  • Steroid/stress Associated Neutrophilia
  • Physiologic/Excitement Neutrophilia
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12
Q

What is Acute Inflammatory Neutrophilia?

A
  • Expected with significant inflammation of internal or subcutaneous tissue
    • Mediators easily access systemic blood
  • Not expected with lower urinary tract and superficial cutaneous lesions or oral cavity
    • Mediators lost to urine, skin, oral cavity
  • Often not seen with inflammation of the brain or spinal cord
    • Mediators do not leave the protected environment
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13
Q

What is Chronic Inflammatory Neutrophilia?

A
  • Mediated by: Cytokines from inflammatory site ongoing for at least 1 week
    • Mature neutrophilia - little or no left shift
    • increased neutrophil release from storage pool
    • Increased migration to tissues
    • Granulocytic Hyperplasia
  • Does NOT always follow an acute inflammatory neutrophilia, even if the stimulus persists & there is some development of granulocytic hyperplasia seen when looking at the marrow
    • If stimulus is severe or increases in intensity a left shift may persist or increase
  • “Chronic” refers to the development of granulocytic hyperplasia and the bone marrow ‘catching up’
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14
Q

What is Glucocorticoid-associated (“Stress”) Neutrophilia

A
  • Common
  • Mediated by cortisol, prednisone, prednisolone
  • Neutrophilia w/ NO left shift
    • may see hyper-segmented neutrophils (5+ lobes)
    • Shift from Marginating to Circulating pool
    • Increased release from storage pools
    • Decreased migration to tissues
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15
Q

What is Excitement/Physiologic Neutrophilia

A
  • Especially in Cats where the Marginating Pool is ~3x Circulating Pool
  • Mediated by: Catecholamines (epi/norepi)
  • Causes a Mature neutrophilia
    • Shift from marginating to circulating pool
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16
Q

What are the mechanisms of Neutropenia?

A
  • Severe, overwhelming acute inflammatory neutropenia
  • Endotoxin neutropenia
  • Granulocytic hypoplasia
  • Ineffective Production
  • Peripheral destruction - rare
    *
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17
Q

What is Severe, overwhelming, acute inflammatory neutropenia?

A
  • Mediated by: Cytokines from inflammatory site
    • Increased release of neutrophils from storage & maturation pools
    • Neutropenia with left shift
    • Increased migration to tissue
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18
Q

When does neutropenia occur?

A

Neutropenia occurs because migration of neutrophils to inflamed tissue exceeds the release of neutrophils from the marrow

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19
Q

How do endotoxins cause Neutropenia?

A
  • Endotoxins and Cytokines stimulate sequestration of neutrophils in the marginating pool
  • Will be seen as Acute Overwhelming Inflammatory Neutropenia
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20
Q

What is Granulocytic Hypoplasia Neutropenia?

A
  • Occurs when marrow cells or cells or the microenvironment are damaged
  • Marrow disease causing decreased neutrophil production (decreased granulopoiesis)
    • Infections, neoplastic, toxic, necrosis, myelofibrosis, drugs
  • Persistent neutropenia
    • Usually NO left shift - may be present in infections or if the marrow is starting to produce cells
    • Maturation is complete and orderly but decreased
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21
Q

What is Ineffective Production Neutopenia?

A
  • Occurs when neutrophils precursors are defective/damaged & die BEFORE release
  • Diseases causing defective/ineffective granulopoiesis
    • immune-mediated, drugs, G-CSF deficiency
  • Lack of orderly and complete maturation of neutrophil sequence
  • Maturation arrest commonly seen when
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22
Q

What are some of the species differences when it comes to neutrophilia and neutropenia?

A
  • Dogs:
    • High marrow reserve
    • Rapid regenerative capacity
    • Neutrophilia up to 120,000 u/L
    • Neutropenia in acute inflammation is a very sever lesion
  • Cats:
    • Intermediate Marrow Reserve
    • Intermediate regenerative capacity
    • Neutrophilia up to 60,000 u/L
    • Neutropenia in acute inflammation is a very severe lesion
  • Horses:
    • Similar to cats
    • Neutrophilia up to 30,000 u/L
    • Neutropenia in acute inflammation is a probable severe lesion
  • Cattle:
    • Low Marrow reserves
    • Slow Regenerative capacity
    • Neutrophilia up to 25,000 u/L
    • Neutropenia is a common finding regardless of severity as marrow reserves are low
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23
Q

What is different about neutropenia in Cattle?

Study These Flashcards
A
  • Acute inflammatory lesions consume neutrophils from blood and & marrow within hours
    • results in neutropenia that lasts a few days
  • After that time, repopulation of blood with neutrophils with a left shift, occurs as the marrow production increases
24
Q

What are the kinetics of Lymphocytes?

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A
  • Relatively long lived cells, some very long
    • Weeks, months, years
  • Retain ability to divide
  • Recirculate - between lymph nodes and other lymphoid organs/tissues
    • Average transit time in blood is 30 minutes
    • Total recirculation time varies - 1 to several hours
  • Although plasma cells are differentiated B-cells, we do NOT see plasma cells in the blood in health
25
What are the causes of Lymphocytosis?
* Chronic inflammation - lymphopoiesis d/t chronic antigenic stimulation * Physiologic lymphocytosis (catecholamines) * Lymphoid neoplasia
26
What is Chronic inflammation Lymphocytosis?
* Part of **hyperplastic lymphoid response** * Chronic antigenic or cytokine stimulation * increases production of lymphocytes * May see reactive lymphocytes in blood * Concurrent Leukogram abnormalities: * Neutrophilia (usually mature) * Monocytosis * +/- eosinophilia and/or basophilia * Causes: * Bacterial infections (E. coli) * Fungal infections, primarily systemic * Viral infections (FeLV) * Protozoal infections, especially babesial and theilerial
27
What are reactive lymphocytes?
* Immune stimulated lymphocytes * Occur in upregulated synthesis * inflammatory mediators * immunoglobulins (antibodies) * Active, systemic antigenic stimulation secondary to both infectious & noninfectious disorders * defects include: * Hyperchromatic nucleus * Scant basophilic cytoplasm * Hyperchromatic cleaved nucleus * Prominent Goli zone * Cytoplasmic basophilia * Irregularly shaped nucleus
28
What is Physiologic Lymphocytosis?
* Shift from marginating to circulating pool * Usually lasts minutes to hours * Morphologic changes in lymphocytes are NOT expected * Causes: (Catecholamines) * Fight or Flight response * Catecholamine injections
29
What is Lymphocytosis due to Lymphoid neoplasia?
* Neoplastic Transformation can occur in any tissue * Increased production of neoplastic lymphocytes in _bone marrow_ (**leukemia)** * Increased production of neoplastic lymphocytes in the tissues or lymph nodes (**lymphoma)** * Usually atypical, often medium or large lymphocytes in circulation
30
What causes Lymphopenia?
* **Acute Inflammation** * **Corticosteroids** * Lymphoid aplasia or hypoplasia * Depletion
31
What is Acute Inflammatory Lymphopenia?
* Most acute inflammatory leukograms (neutrophilia & left shift) also have lymphopenia * Increased migration of lymphocytes to inflamed tissue * Decreased migration of lymphocytes from LN to blood * “Homing” of lymphocytes to LN
32
What is Steroid lymphopenia?
* Entire steroid leukogram: * Mature neutrophilia, lymphopenia, +/- monocytosis and/or eosinopenia * Decreased Lymphopoiesis * Cytotoxic effects in those produced * Decreased efflux from LN * intermediate shift from Circulating pool to bone marrow and LN
33
What are the Kinetics of Monocytes?
* **No marrow storage pool** * Circulating and Marginal Pools * Migrate into tissues * Blood transit time: ~18-24 hr * Become macrophages, dendritic cells etc. * Stem cell shared with neutrophils * Phagocytose in tissue * Rarely see phagocytosis in peripheral blood smear * In cytology - “mononuclear cells”
34
What is a Macrophage?
* Have more granules & proteolytic enzymes than monocytes * Phagocytic activity * Long-lived and can divide at least once in tissues
35
What is Monocytosis?
* Similar response as neutrophils - share a stem cell * Not pathognomonic for anything in particular * Present in Acute & chronic inflammation * cytokine stimulation * Steroid response * Dogs\>cats\>horses & cattle
36
Is monocytopenia concerning?
Usually not significant if present
37
What are eosinophils?
* Contain proteins that bind & damage parasite membranes * Important in allergic inflammation & immune-complex reactions * Some phagocytic ability * ineffective and not protective against bacterial infections
38
What are the kinetics of eosinophils?
* Blood transit time: **30m - 12hr** * Long-lived in subepithelial locations * lungs, skin, GI, uterus * Can get **massive tissue accumulations** in tissues without an eosinophilia * In health: 200-400 eosinophils in tissue for each 1 in blood
39
What causes Eosinophilia?
* Hypersensitivity * Parasitic diseases * Mast cell degranulation (neoplasia or inflammatory) * Addison's disease (hypoadrenocorticism) * Hypereosinophilic syndrome * Paraneoplastic eosinophilia (chemoattractant agents in the neoplastic tissue) * Others
40
What causes Eosinopenia?
* Difficult to recognize * By itself is of little diagnostic significance * Corticosteroids: * Stress leukogram * Hyperadrenocorticism (Cushings)
41
What are Basophils?
* Blood concentrations are low * very low in dogs/cats * higher in ruminants/equids * Contain histamine & heparin * Role in Type-1 Hypersensitivity * Role in delayed-type hypersensitivity * **Proinflammatory cells**
42
What causes Basophilia?
* Rare * Hypersensitivity * Parasitic disease * Neoplasia
43
What causes basopenia?
cannot be documented with routine leukocyte differential counts
44
What is the function of Mast Cells?
* Promote hypersensitivity reactions * Stimulate T cells * Host defense against parasites * Promote acute and chronic inflammatory responses
45
Where are mast cells located?
* Occasionally seen in peripheral blood * Inflammation * Mast cell neoplasia * Often in tissue (cytologic preparations * Inflammation * Mast cell neoplasia
46
What is a Leukogram?
* Includes all tests on the CBC that evaluate WBC, including the following: * **Assessment of leukocyte numbers**: * total WBC count (all cell types) * Relative (%) differential leukocyte count * Absolute (cells/uL) differential leukocyte count * **WBC morphologic features:** * Morphology can give clues as to underlying disease pathogenesis
47
What supplies are needed for a Leukogram?
* Properly collected and handled blood * Anticoagulated blood * EDTA - mammals * Heparin - Avian/reptiles * Total WBC * Well-made blood smear * Differential cell counts * Cell morphology evaluation
48
How is a manual WBC differential done?
* Count at least 100 cells (200-500 better) in the monolayer * Segs * bands * lymphocytes * Monocytes * Eosinophils * Basophils * Others * Differentiate WBCs into groups * Determine WBC percentage * Multiply % times WBC * Product is individual leukocyte concentration
49
What are some of the classic Leukogram patterns?
* Normal * Physiologic leukocytosis (excitement) * Stress/corticosteroid leukogram * Severe, overwhelming, acute inflammatory leukogram * Chronic inflammatory leukogram * Leukamoid (extreme neutrophilic leukocytosis) * Neutrophils \>50,000 * Eosinophilic inflammation * Leukemia (discussed later)
50
What is the leukogram pattern of Acute inflammation?
* Total WBC: **⇡** * Segs: **⇡** * Non-segs: **⇡** * Lymph: **⇣** * Mono: WRI - **⇡** * Eos: **⇣ -** WRI
51
What is the leukogram pattern of Physiologic leukocytosis?
* Total WBC: ⇡ * Segs: ⇡ * Non-segs: WRI * Lymph: ⇡ * Mono: WRI - ⇡ * Eos: WRI
52
What is the pattern of Stress/Corticosteroid leukogram?
* Total WBC: ⇡ * Segs: ⇡ * Non-segs: WRI - ⇡ * Lymph: ⇣ * Mono: ⇡ * Eos: **⇣**
53
What is the leukogram pattern of Chronic inflammation ?
* Total WBC: ⇡ * Segs: ⇡ * Non-segs: WRI - ⇡ * Lymph: ⇡ * Mono: ⇡ * Eos: WRI
54
What is the Leukogram pattern of acute overwhelming inflammation?
* Total WBC: ⇣ * Segs: ⇣ * Non-segs: WRI - ⇡ * Lymph: ⇣ * Mono: WRI * Eos: ⇣ - WR
55
How does Acute inflammation affect ruminants?
* In health Lymphocytes \> Neutrophils * Small storage pool of neutrophils in bone marrow * Often neutropenia and degenerative left shift
56
How does chronic inflammation affect ruminants?
* Granulocytic hyperplasia * Neutrophilia +/- left shift * Evidence of granulocytic hyperplasia takes at **least 5 days** to become evident in peripheral blood (neutrophilia)
57
What changes in the leukogram suggest improvement?
* Leukocytosis ⇢ return towards Ref interval * Leukopenia ⇢ return towards Ref Interval

Clinical Pathology (12 decks)

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