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Hem/Onc > Leukocyte Evaluation and Disorders > Flashcards

Leukocyte Evaluation and Disorders Flashcards

1
Q

any of a number of substances (interferon, interleukin, and growth factors) that are secreted by cells of the immune system and have an effect on other cells

A

cytokines

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2
Q

a biological cell that descends from a stem cell and can differentiate into a specific type of “target” cell

A

progenitor

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3
Q

Reduced # of neutrophils, eosinophils, and basophils

A

Granulocytopenia

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4
Q

Complete absence of neutrophils, eosinophils, and basophils

A

Agranulocytosis

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5
Q

what WBC are Granulocytes and Agranulocytes

A
  1. Granulocytes – neutrophils, basophils, eosinophils
    - Polymorphonuclear (PMN) leukocytes
    - Characterized by the staining pattern of the granules
  2. Agranulocytes - lymphocytes, monocytes
    - Mononuclear leukocytes
    - Absence of staining granules
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6
Q

a white blood cell with secretory granules in its cytoplasm

A

Granulocytes

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7
Q

Originates from the hematopoietic stem cell (HSC)

A

Self-renewal

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8
Q

HSC are able to do what

A
  1. self-replicate (self-renew)
  2. differentiate
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9
Q

what is the proliferation stage of Granulocyte Hematopoiesis

A

Myeloblast → promyelocyte → myelocytes
Capable of cell division and differentiation

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10
Q

what is the differentiation stage

A

Metamyelocyte → band → polymorphonuclear (PMN) cells
- metamyelocytes and bands are immature granulocytes
- polymorphonuclear cells are mature granulocytes
- cells are able to mature and differentiate but no division

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11
Q

cells from differentiation stage are able to ?

A

mature and differentiate but not capable of division

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12
Q

cells in proliferation stage are able to do what that they cant do in differentiation stage?

A

Capable of cell division and differentiation

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13
Q

what are you looking at in a WBC diff interpretation

A
  1. neutrophil count or (mature + immature neutrophil)
  2. absolute vs relative
    - absolute - # of cells (more reliable in pathologic states)
    - relative - % of leukocytes
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14
Q

what value is more reliable in pathologic states

A

absolute value

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15
Q

? is needed to determine morphology and will confirm presence of immature cells if not provided on the CBC

A

peripheral smear

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16
Q

protects the body from bacterial and fungal infection by inducing cell death

A

neutrophils

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17
Q

Progenitor matures where and for how long?

A

marrow
7-10 d

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18
Q

during a steady state, most neutrophils never ?

A

enter blood stream

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19
Q

what is the “storage pool”

A

in the marrow to be called upon in times of need

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20
Q

what is the “circulation pool”

A

½ of neutrophils circulate in blood <24 hrs before entering into the tissue to be used for up to 1-2 days in tissue
also known as extramedullary neutrophils

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21
Q

what is the “marginal pool”

A

Appx ½ are attached to the endothelial walls
(extramedullary neutrohils)

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22
Q

Elevated absolute neutrophil count is known as ?

A

neutrophilia aka granulocytosis

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23
Q

2 possible neutrophilic presentations

A
  1. neutrophilic shift
  2. true neutrophilia
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24
Q

Neutrophils from the marginal pool shift to circulating pool is known as ?

A

neutrophilic shift

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25
Q

onset of neutrophilic shift

A

transient - within 1-2 min, lasting 20-30 min

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26
Q

acute physical/emotional stress can cause what type of neutrophilic presentation

A

neutrophilic shift
1. exercise
2. seizure
3. paroxysmal tachycardia
4. epinephrine injection
5. post-op state

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27
Q

Release of neutrophils from storage pool (marrow) is what type of neutrophil presentation

A

true neutrophilia

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28
Q

3 etiologic classifications of true neutrophilia

A
  1. Spurious - falsely elevated neutrophils
  2. Primary - often from inherited defect
  3. Secondary to acquired condition - most common
    - MC cause - infectious etiology
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29
Q

Severe infections can result in early release of bands known as ?

A

left shift

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30
Q

3 types of neutropenia

A

neutrophilia: ANC < 1800 cells/µL (1.8 x ×10³/µL )

  1. Mild neutropenia – ANC >1000 and <1800 cells/µL
  2. Moderate neutropenia – ANC >500 and <1000 cells/µL
  3. Severe neutropenia – ANC <500 cells/µL
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31
Q

what are the 3 pathophysiologic processes of neutropenia

A
  1. Insufficient or injured bone marrow stem cells
  2. Shifts in neutrophils from the circulating pool to the marginal blood or tissue pools
  3. Increased destruction in the circulation
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32
Q

neutropenia often exacerbated by various medications and more often seen with morning specimens is known as ?

A

pseudoneutropenia

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33
Q

Mc demographics of neutropenia

A
  1. elderly
  2. ethnic groups (i.e African American, Asians) may have low counts
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34
Q

complication with neutropenia

A

bacterial infection
1. Initial presenting s/s may be absent due to the decrease in neutrophils
- Ex: warmth/swelling, pus, abdominal pain, infiltrate on chest radiography
2. serious infections occur with ANC < 500/µL

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35
Q

what medications can cause neutropenia?

A
  1. sulfonamides
  2. PCN
  3. cephalosporins
  4. cimetidine
  5. chlorpromazine
  6. procainamide
  7. methimazole
  8. phenytoin
  9. chlorpropamide
  10. antiretroviral medications
  11. rituximab
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36
Q

additional work up + standard tx for neutropenia

A
  • Work-up:
  • Bone marrow biopsy: determines the state of the granulocyte precursors
  • (+) serum antineutrophil antibodies = autoimmune neutropenia if bone marrow is normal
  • (+) Rheumatoid factor and splenomegaly (via US/CT) = Felty syndrome
  • Standard tx:
    1. Myeloid growth factors
  • Goal - increase neutrophil production
  • Granulocyte colony-stimulating factor (G-CSF)
  • Granulocyte-macrophage colony stimulating factor (GM-CSF)
    2. additional tx depends on cause
  • Medication induced
  • Autoimmune neutropenia
  • Myelosuppressive chemotherapy induced neutropenia
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37
Q

Refer to hematology if ANC is

A

persistently below 1000 cells/µL

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38
Q

filgrastim (Neupogen)
pegfilgrastim (Neulasta)

A

Granulocyte colony-stimulating factor (G-CSF)

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39
Q

filgrastim (Neupogen)
pegfilgrastim (Neulasta)

A

Granulocyte colony-stimulating factor (G-CSF)

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40
Q

sargramostim (Leukine)

A

Granulocyte-macrophage colony stimulating factor (GM-CSF)

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41
Q

if a pt has a neutropenic fever what determines if they get outpatient or inpatient tx?

A
  • ANC >1000 cells/µL = outpatient basis
  • ANC of <500 cells/µL = inpatient treatment with parenteral antibiotics
  • ANC 500-1000 cells/µL = management is case based
42
Q

if the neutropenia is medication induced, what is the management?

A

D/C causative agent

43
Q

if the neutropenia is autoimmune induced, what is the management?

A

pulse steroids + intermittent dosing of myeloid growth factors

44
Q

if myelosuppressive chemotherapy induces neutropenia, what is the management?

A

myeloid growth factor +/- prophylactic antimicrobials if intense therapy

45
Q

if a pt has bacterial infections without a clinical response to antibiotics within 24 to 48 hours, what is the tx?

A

granulocyte transfusion

46
Q

primarily tissue dwellers
assist in fighting parasites, allergies and asthma

A

eosinophils

47
Q

what are the Mc target organs for eosinophils

A

skin
airway
GI tract

48
Q

3 cytokines responsible for eosinophil development and differentiation

A
  1. IL-5
  2. IL-3
  3. granulocyte-macrophage colony-stimulating factor (GM-CSF)
49
Q

what is the lifespan of eosinophils

A
  1. Circulate for 8–12 hours before entering into a dwelling tissue
  2. Remain in tissue on average 1-2 weeks
50
Q

The tissue lifespan of eosinophils ranges from ?

A

2 to 5 days.

51
Q

what can increase eosinophil survival and for how long?

A

cytokines
14+ days

52
Q

2 types of eosinophilia
describe both

A
  1. primary - clonal or idiopathic
    - clonal - genetic mutation or malignancy
    - idiopathic when all other causes have been ruled out - Hypereosinophilic syndrome (HES)
  2. secondary - reactive underlying etiology
53
Q

what is the pathophysiology of eosinophil

A

dysregulation (overproduction) of the cytokines (IL 3, IL 5, GM-CSF) results in an increased eosinophil production and/or eosinophil longevity

54
Q

what is the MC complication from eosinophilia

A
  1. tissue damage
    - most likely to occur with absolute eosinophil counts > 1500/µL
    - MC in: skin, airway, and GI tract
55
Q

organ damage from eosinophilia results from: (3)

A
  1. Release of toxic granule products that can damage epithelial cells and nerves
  2. Production of lipid mediators which control smooth muscle contraction and recruitment of inflammatory cells
  3. Release of cytokines which may be involved in tissue remodeling and fibrosis
56
Q

which WBC:
- Contain heparin - help prevent clotting
- Release histamine during contact with allergens
- Suspected function of IgE antibody formation and activation

A

basophils

57
Q

MC causes of basophilia

A
  1. primary: chronic myelogenous leukemia (CML)
  2. secondary:
    - myeloproliferative disorders (polycythemia rubra vera, myelofibrosis, thrombocythemia)
    - hypersensitivity or inflammatory reactions
    - hypothyroidism
58
Q

a small leukocyte with a single round nucleus and receptor molecules on the surface to bind to antigens and remove them

A

lymphocyte

59
Q

3 lymphocyte classes

A
  1. T-cell - 60-80%
  2. B-cell - 10-20%
  3. natural killer cells (NK) - 5-10%
60
Q

what type of lymphocyte can differentiate into plasma cells

A

B-cells

61
Q

which lymphocytes are mature cells that can divide on demand?

A

T-cell
B-cell

62
Q

T-cells develop and differentiate where?

A

thymus

63
Q

after T-cells have matured, where do they get exported?

A

blood and secondary lymphoid tissues

64
Q

which lymphocyte destroys human cells that have been attacked by viruses or have become cancerous

A

T-cells

65
Q

3 categories of T-cell lymphocytes

A
  1. Helper T cells - aka “CD 4+ T-cell”- recognizes foreign antigens and stimulates antibody production; produces cytokines that activate other T-cells
  2. Cytotoxic T cells - aka “CD8+ T-cell” - attacks and destroys foreign cells
  3. Regulatory T cells - turns off immune response of other T-cells preventing autoimmune responses
66
Q

secondary lymphoid tissues are:

A
  1. lymph nodes
  2. spleen
  3. tonsils
  4. aggregations of lymphoid tissue located in the gastrointestinal and respiratory tracts
67
Q

where do B-cells mature?

A

bone marrow

68
Q

functions of B-cells

A
  1. capture, internalize and present antigens to the T cells to initiate T-cell immune responses
  2. express surface immunoglobulin (Ig) receptors to specific antigens
  3. can become memory B cells = providing long-lasting immunity over decades
  4. precursor to plasma cell
69
Q

a fully differentiated lymphocyte with a short life that produces a large number of antibodies (immunoglobulins) until active infectious agent is removed

A

plasma cell

70
Q
  • contains cytotoxic granules which attacks cancerous or virally infected cells while awaiting immune response from cytotoxic T-cells
  • receives signals from foreign cell - doesn’t require an initiating immune system activiation
A

NK cells

71
Q

Helps maintain control of immune response by recognizing cells as foreign or “self”

A

NK cells

72
Q

Defined as an elevated lymphocyte count above upper limit of normal (ULN) for age range

A

lymphocytosis

73
Q

2 categories for lymphocytic disorders

A
  1. Monoclonal lymphocytosis
    - benign or lymphoproliferative disorder
  2. Polyclonal lymphocytosis
    - infectious, transient, reactive, benign
74
Q

An expanded clonal B-cell population in the blood without any sign of infection, autoimmune process or lymphoproliferative disorder

A

Monoclonal lymphocytosis

75
Q

2 etiologies of monoclonal lymphocytosis

A
  1. Premalignant
    - monoclonal B cell lymphocytosis (MBL)
  2. Malignant
    - Chronic Lymphocytic Leukemia (CLL)
    - Non-Hodgkin Lymphoma (NHL) with circulating disease
    - Hairy Cell Leukemia (HCL)
    - Large Granular Lymphocytic Leukemia (LGL)
76
Q

associated with underlying condition expected to normalize within 2 months after resolution of condition

A

Polyclonal lymphocytosis

77
Q

etiologies of Polyclonal lymphocytosis

A
  1. Infectious:
    - MC - viral infections (MC - mononucleosis)
    - Other infections - Pertussis, cat-scratch disease and toxoplasmosis
  2. Transient
    - emotion or physical stress, acute illness/surgery
  3. Reactive
    - drug hypersensitivity reaction
  4. Benign persistent
    - persistent polyclonal B cell lymphocytosis, post-splenectomy, thymoma
78
Q

how do you work up lymphocytosis?

A
  1. repeat CBC - rule out lab errors
  2. peripheral blood smear - see any presence of abnormal morphologies
  3. flow cytometry - detects surface antigens specific to B- or T-cells to detect clonal lymphocyte proliferation
79
Q

if there is an obvious viral infection that is causing lymphocytosis, what do you NOT order?

A

flow cytometry

80
Q

an Absolute Lymphocyte Counts (ALC) below the lower threshold, which differs by age

A

lymphocytopenia

81
Q

pathogenesis of lymphocytopenia

A
  1. decreased production
  2. increased destruction
  3. lymphocytes become lodged in the spleen or lymph nodes
82
Q

sequelae of lymphocytopenia

A
  1. opportunistic infections
  2. increased risk of malignancy and autoimmune disorders
83
Q

etiology of lymphocytopenia

A
  1. Inherited - stem cell abnormality = ineffective lymphopoiesis
  2. Acquired
    1) Infectious disease
    - HIV - destruction of CD+4 T cells
    - other viral infections - transient reduction resolves after resolution of virus
    2) Iatrogenic
    - radiotherapy, cytotoxic chemotherapy, glucocorticoids, antilymphocyte globulin (anti-rejection) or alemtuzumab (anti-neoplastic/multiple sclerosis)
    3) Autoimmune disorders
    4) Nutritional deficiency
    - Zinc deficiency
    - chronic ETOH use
84
Q

lifecycle of monocyte

A

remain in circulation for 1-3 days before entering tissues where they differentiate into macrophages or dendritic cells

85
Q

Half of total monocyte count is stored in the ___ as a reserve

A

spleen

86
Q

function of monocytes

A
  1. phagocytosis - digest and destruct microbes (innate immunity)
  2. antigen presentation - monocytes capture antigens and present them on the cell surface allowing:
    - T-cell recognition
    - activation & immune response (adaptive immunity)
  3. inflammatory cytokine production = innate immune response
87
Q

monocytosis most often results from ?

A

a transient condition that isn’t from dysfunction of hematopoietic process

88
Q

etiologies of monocytosis

A
  1. MC - bacterial infections complicated by neutropenia
  2. Acute/chronic monocytic leukemias/lymphomas
  3. Asplenia
  4. Inflammatory/autoimmune conditions
  5. Treatment with corticosteroids or colony stimulating factors
89
Q

leukopenia tx options

A
  1. Broad spectrum antibiotics - prevent infections
  2. Myeloid growth factors - stimulate cellular proliferation/differentiation
    - G-CSFs
    - GM-CSFs
  3. Corticosteroid therapy - immune-mediated neutropenia
  4. Correction of nutritional (vit B12 or folic acid) deficiency if detected
  5. Splenectomy
  6. diet
  7. patient education

(geared towards underlying condition)

90
Q

Splenectomy is reserved for ?

A

chronic neutropenia unresponsive to other treatments - complicated by recurrent life-threatening bacterial infections

91
Q

what is the diet management for leukopenia

A
  1. Avoid raw and undercooked meat or well water
  2. Avoid all unpasteurized foods/liquids
  3. Avoid aged cheese and cheese-based dressings
  4. Avoid unwashed raw fruits and vegetables
  5. Avoid exposure to fresh flowers (due to germs in the soil)
  6. Avoid consumption of all outdated/molded products
92
Q

pt education for leukopenia tx/management

A
  1. Appropriate hand washing and care of indwelling catheters
  2. Avoid rectal manipulation (temps, suppositories, enemas)
93
Q

indications for Leukocyte Analysis

A

leukocytosis
leukocytopenia

94
Q

Leukocyte Analysis results depend on ?

A

experienced technique
Sources of error - mechanical trauma to the cells during preparation of the thin blood film slide

95
Q

a peripheral smear that has PMN leukocytes that have 5-6+ lobes

A

hypersegmentation
- most often with megaloblastic anemias, sometimes with myeloproliferative disorders, or following chemotherapy (methotrexate)

96
Q

a peripheral smear seen most often with bacterial infections and in association with cytoplasmic vacuolization

A

granulation

97
Q

a peripheral smear showing Irregularly shaped blue staining area in the cytoplasm; seen with infections

A

Döhle body

98
Q

a peripheral smear showing an artifact of EDTA anticoagulation, this may cause the platelet count to be artifactual low

A

platelet satellitosis

99
Q

A process that measures cellular properties as they are moving in a fluid stream, past a stationary set of laser detectors

A

Flow Cytometry Immunophenotyping

100
Q

What:
- Detects antigens or markers on the surface of the cells
- Differentiates normal cells from malignant cells

A

Flow Cytometry Immunophenotyping

101
Q

benefits of Flow Cytometry Immunophenotyping

A

quick procedure / interpretation

102
Q

what types of tissues can be assessed by Flow Cytometry Immunophenotyping

A
  1. blood
  2. bone marrow
  3. lymph node tissue

Hem/Onc (13 decks)

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