Leukocyte Evaluation and Disorders Flashcards
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
cytokines
a biological cell that descends from a stem cell and can differentiate into a specific type of “target” cell
progenitor
Reduced # of neutrophils, eosinophils, and basophils
Granulocytopenia
Complete absence of neutrophils, eosinophils, and basophils
Agranulocytosis
what WBC are Granulocytes and Agranulocytes
- Granulocytes – neutrophils, basophils, eosinophils
- Polymorphonuclear (PMN) leukocytes
- Characterized by the staining pattern of the granules - Agranulocytes - lymphocytes, monocytes
- Mononuclear leukocytes
- Absence of staining granules
a white blood cell with secretory granules in its cytoplasm
Granulocytes
Originates from the hematopoietic stem cell (HSC)
Self-renewal
HSC are able to do what
- self-replicate (self-renew)
- differentiate
what is the proliferation stage of Granulocyte Hematopoiesis
Myeloblast → promyelocyte → myelocytes
Capable of cell division and differentiation
what is the differentiation stage
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
cells from differentiation stage are able to ?
mature and differentiate but not capable of division
cells in proliferation stage are able to do what that they cant do in differentiation stage?
Capable of cell division and differentiation
what are you looking at in a WBC diff interpretation
- neutrophil count or (mature + immature neutrophil)
- absolute vs relative
- absolute - # of cells (more reliable in pathologic states)
- relative - % of leukocytes
what value is more reliable in pathologic states
absolute value
? is needed to determine morphology and will confirm presence of immature cells if not provided on the CBC
peripheral smear
protects the body from bacterial and fungal infection by inducing cell death
neutrophils
Progenitor matures where and for how long?
marrow
7-10 d
during a steady state, most neutrophils never ?
enter blood stream
what is the “storage pool”
in the marrow to be called upon in times of need
what is the “circulation pool”
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
what is the “marginal pool”
Appx ½ are attached to the endothelial walls
(extramedullary neutrohils)
Elevated absolute neutrophil count is known as ?
neutrophilia aka granulocytosis
2 possible neutrophilic presentations
- neutrophilic shift
- true neutrophilia
Neutrophils from the marginal pool shift to circulating pool is known as ?
neutrophilic shift
onset of neutrophilic shift
transient - within 1-2 min, lasting 20-30 min
acute physical/emotional stress can cause what type of neutrophilic presentation
neutrophilic shift
1. exercise
2. seizure
3. paroxysmal tachycardia
4. epinephrine injection
5. post-op state
Release of neutrophils from storage pool (marrow) is what type of neutrophil presentation
true neutrophilia
3 etiologic classifications of true neutrophilia
- Spurious - falsely elevated neutrophils
- Primary - often from inherited defect
- Secondary to acquired condition - most common
- MC cause - infectious etiology
Severe infections can result in early release of bands known as ?
left shift
3 types of neutropenia
neutrophilia: ANC < 1800 cells/µL (1.8 x ×10³/µL )
- Mild neutropenia – ANC >1000 and <1800 cells/µL
- Moderate neutropenia – ANC >500 and <1000 cells/µL
- Severe neutropenia – ANC <500 cells/µL
what are the 3 pathophysiologic processes of neutropenia
- Insufficient or injured bone marrow stem cells
- Shifts in neutrophils from the circulating pool to the marginal blood or tissue pools
- Increased destruction in the circulation
neutropenia often exacerbated by various medications and more often seen with morning specimens is known as ?
pseudoneutropenia
Mc demographics of neutropenia
- elderly
- ethnic groups (i.e African American, Asians) may have low counts
complication with neutropenia
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
what medications can cause neutropenia?
- sulfonamides
- PCN
- cephalosporins
- cimetidine
- chlorpromazine
- procainamide
- methimazole
- phenytoin
- chlorpropamide
- antiretroviral medications
- rituximab
additional work up + standard tx for neutropenia
- 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
Refer to hematology if ANC is
persistently below 1000 cells/µL
filgrastim (Neupogen)
pegfilgrastim (Neulasta)
Granulocyte colony-stimulating factor (G-CSF)
filgrastim (Neupogen)
pegfilgrastim (Neulasta)
Granulocyte colony-stimulating factor (G-CSF)
sargramostim (Leukine)
Granulocyte-macrophage colony stimulating factor (GM-CSF)
if a pt has a neutropenic fever what determines if they get outpatient or inpatient tx?
- 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
if the neutropenia is medication induced, what is the management?
D/C causative agent
if the neutropenia is autoimmune induced, what is the management?
pulse steroids + intermittent dosing of myeloid growth factors
if myelosuppressive chemotherapy induces neutropenia, what is the management?
myeloid growth factor +/- prophylactic antimicrobials if intense therapy
if a pt has bacterial infections without a clinical response to antibiotics within 24 to 48 hours, what is the tx?
granulocyte transfusion
primarily tissue dwellers
assist in fighting parasites, allergies and asthma
eosinophils
what are the Mc target organs for eosinophils
skin
airway
GI tract
3 cytokines responsible for eosinophil development and differentiation
- IL-5
- IL-3
- granulocyte-macrophage colony-stimulating factor (GM-CSF)
what is the lifespan of eosinophils
- Circulate for 8–12 hours before entering into a dwelling tissue
- Remain in tissue on average 1-2 weeks
The tissue lifespan of eosinophils ranges from ?
2 to 5 days.
what can increase eosinophil survival and for how long?
cytokines
14+ days
2 types of eosinophilia
describe both
- primary - clonal or idiopathic
- clonal - genetic mutation or malignancy
- idiopathic when all other causes have been ruled out - Hypereosinophilic syndrome (HES) - secondary - reactive underlying etiology
what is the pathophysiology of eosinophil
dysregulation (overproduction) of the cytokines (IL 3, IL 5, GM-CSF) results in an increased eosinophil production and/or eosinophil longevity
what is the MC complication from eosinophilia
- tissue damage
- most likely to occur with absolute eosinophil counts > 1500/µL
- MC in: skin, airway, and GI tract
organ damage from eosinophilia results from: (3)
- Release of toxic granule products that can damage epithelial cells and nerves
- Production of lipid mediators which control smooth muscle contraction and recruitment of inflammatory cells
- Release of cytokines which may be involved in tissue remodeling and fibrosis
which WBC:
- Contain heparin - help prevent clotting
- Release histamine during contact with allergens
- Suspected function of IgE antibody formation and activation
basophils
MC causes of basophilia
- primary: chronic myelogenous leukemia (CML)
- secondary:
- myeloproliferative disorders (polycythemia rubra vera, myelofibrosis, thrombocythemia)
- hypersensitivity or inflammatory reactions
- hypothyroidism
a small leukocyte with a single round nucleus and receptor molecules on the surface to bind to antigens and remove them
lymphocyte
3 lymphocyte classes
- T-cell - 60-80%
- B-cell - 10-20%
- natural killer cells (NK) - 5-10%
what type of lymphocyte can differentiate into plasma cells
B-cells
which lymphocytes are mature cells that can divide on demand?
T-cell
B-cell
T-cells develop and differentiate where?
thymus
after T-cells have matured, where do they get exported?
blood and secondary lymphoid tissues
which lymphocyte destroys human cells that have been attacked by viruses or have become cancerous
T-cells
3 categories of T-cell lymphocytes
- Helper T cells - aka “CD 4+ T-cell”- recognizes foreign antigens and stimulates antibody production; produces cytokines that activate other T-cells
- Cytotoxic T cells - aka “CD8+ T-cell” - attacks and destroys foreign cells
- Regulatory T cells - turns off immune response of other T-cells preventing autoimmune responses
secondary lymphoid tissues are:
- lymph nodes
- spleen
- tonsils
- aggregations of lymphoid tissue located in the gastrointestinal and respiratory tracts
where do B-cells mature?
bone marrow
functions of B-cells
- capture, internalize and present antigens to the T cells to initiate T-cell immune responses
- express surface immunoglobulin (Ig) receptors to specific antigens
- can become memory B cells = providing long-lasting immunity over decades
- precursor to plasma cell
a fully differentiated lymphocyte with a short life that produces a large number of antibodies (immunoglobulins) until active infectious agent is removed
plasma cell
- 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
NK cells
Helps maintain control of immune response by recognizing cells as foreign or “self”
NK cells
Defined as an elevated lymphocyte count above upper limit of normal (ULN) for age range
lymphocytosis
2 categories for lymphocytic disorders
- Monoclonal lymphocytosis
- benign or lymphoproliferative disorder - Polyclonal lymphocytosis
- infectious, transient, reactive, benign
An expanded clonal B-cell population in the blood without any sign of infection, autoimmune process or lymphoproliferative disorder
Monoclonal lymphocytosis
2 etiologies of monoclonal lymphocytosis
- Premalignant
- monoclonal B cell lymphocytosis (MBL) - Malignant
- Chronic Lymphocytic Leukemia (CLL)
- Non-Hodgkin Lymphoma (NHL) with circulating disease
- Hairy Cell Leukemia (HCL)
- Large Granular Lymphocytic Leukemia (LGL)
associated with underlying condition expected to normalize within 2 months after resolution of condition
Polyclonal lymphocytosis
etiologies of Polyclonal lymphocytosis
- Infectious:
- MC - viral infections (MC - mononucleosis)
- Other infections - Pertussis, cat-scratch disease and toxoplasmosis - Transient
- emotion or physical stress, acute illness/surgery - Reactive
- drug hypersensitivity reaction - Benign persistent
- persistent polyclonal B cell lymphocytosis, post-splenectomy, thymoma
how do you work up lymphocytosis?
- repeat CBC - rule out lab errors
- peripheral blood smear - see any presence of abnormal morphologies
- flow cytometry - detects surface antigens specific to B- or T-cells to detect clonal lymphocyte proliferation
if there is an obvious viral infection that is causing lymphocytosis, what do you NOT order?
flow cytometry
an Absolute Lymphocyte Counts (ALC) below the lower threshold, which differs by age
lymphocytopenia
pathogenesis of lymphocytopenia
- decreased production
- increased destruction
- lymphocytes become lodged in the spleen or lymph nodes
sequelae of lymphocytopenia
- opportunistic infections
- increased risk of malignancy and autoimmune disorders
etiology of lymphocytopenia
- Inherited - stem cell abnormality = ineffective lymphopoiesis
- 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
lifecycle of monocyte
remain in circulation for 1-3 days before entering tissues where they differentiate into macrophages or dendritic cells
Half of total monocyte count is stored in the ___ as a reserve
spleen
function of monocytes
- phagocytosis - digest and destruct microbes (innate immunity)
- antigen presentation - monocytes capture antigens and present them on the cell surface allowing:
- T-cell recognition
- activation & immune response (adaptive immunity) - inflammatory cytokine production = innate immune response
monocytosis most often results from ?
a transient condition that isn’t from dysfunction of hematopoietic process
etiologies of monocytosis
- MC - bacterial infections complicated by neutropenia
- Acute/chronic monocytic leukemias/lymphomas
- Asplenia
- Inflammatory/autoimmune conditions
- Treatment with corticosteroids or colony stimulating factors
leukopenia tx options
- Broad spectrum antibiotics - prevent infections
- Myeloid growth factors - stimulate cellular proliferation/differentiation
- G-CSFs
- GM-CSFs - Corticosteroid therapy - immune-mediated neutropenia
- Correction of nutritional (vit B12 or folic acid) deficiency if detected
- Splenectomy
- diet
- patient education
(geared towards underlying condition)
Splenectomy is reserved for ?
chronic neutropenia unresponsive to other treatments - complicated by recurrent life-threatening bacterial infections
what is the diet management for leukopenia
- Avoid raw and undercooked meat or well water
- Avoid all unpasteurized foods/liquids
- Avoid aged cheese and cheese-based dressings
- Avoid unwashed raw fruits and vegetables
- Avoid exposure to fresh flowers (due to germs in the soil)
- Avoid consumption of all outdated/molded products
pt education for leukopenia tx/management
- Appropriate hand washing and care of indwelling catheters
- Avoid rectal manipulation (temps, suppositories, enemas)
indications for Leukocyte Analysis
leukocytosis
leukocytopenia
Leukocyte Analysis results depend on ?
experienced technique
Sources of error - mechanical trauma to the cells during preparation of the thin blood film slide
a peripheral smear that has PMN leukocytes that have 5-6+ lobes
hypersegmentation
- most often with megaloblastic anemias, sometimes with myeloproliferative disorders, or following chemotherapy (methotrexate)
a peripheral smear seen most often with bacterial infections and in association with cytoplasmic vacuolization
granulation
a peripheral smear showing Irregularly shaped blue staining area in the cytoplasm; seen with infections
Döhle body
a peripheral smear showing an artifact of EDTA anticoagulation, this may cause the platelet count to be artifactual low
platelet satellitosis
A process that measures cellular properties as they are moving in a fluid stream, past a stationary set of laser detectors
Flow Cytometry Immunophenotyping
What:
- Detects antigens or markers on the surface of the cells
- Differentiates normal cells from malignant cells
Flow Cytometry Immunophenotyping
benefits of Flow Cytometry Immunophenotyping
quick procedure / interpretation
what types of tissues can be assessed by Flow Cytometry Immunophenotyping
- blood
- bone marrow
- lymph node tissue
