Leukocyte Eval- Exam 2 Flashcards
______ any of a number of substances, such as interferon, interleukin, and growth factors, that are secreted by certain cells (immune and non-immune) and have an effect on other cells, especially influencing inflammation and growth
cytokine
cytokine have an effect on other cells, especially influencing _____ and _____
inflammation
growth
______ a cell that descends from a stem cell and can differentiate into a specific type of “target” (or “daughter”) cell
Progenitor (cell)
_____ WBC count of >50,000/µL from causes other than leukemia
Leukemoid reaction
Agranulocytosis refers to what kind of cells?
Neutrophils, eosinophils, and basophils
Leukocytes refers to what cells?
Neutrophil
Basophil
Eosinophil
Lymphocyte
Monocyte
_______ Especially active in bacterial and fungal infections by attacking, ingesting, and digesting microorganisms
neutrophil
____ most active in allergies, bacterial and parasitic infections
basophil
______ most active in parasitic infections, allergies, asthma
eosinophil
Eosinophils are more common in ____ than _____
tissues than blood
______ cytotoxic, humoral, and antigen-processing
Especially active against viral infections
lymphocyte
_____ are major cells in the adaptive immune response
lymphocyte
_____ largest WBC, mature into macrophages or dendritic cells. Phagocytosis, antigen processing
Especially active in bacterial infections
Monocyte
Leukocytes with _____ in their cytoplasm, small sacs containing specific enzymes that are released to help further the inflammatory process and to help destroy target antigens/pathogens. What is the bigger category?
secretory granules
granulocytes
granulocytes all stem from _____
myeloblast
Leukocytes with an absence of staining granules in their cytoplasm and a _____. What is the bigger category?
unilobular nucleus
agranulocytes
What do agranulocytes stem from? (Except monocytes they stem from ______
lymphoblast (plasma cells, B lymphocytes, T lymphocytes, NK cells, lymphoid dendritic cells)
myeloblast
_____ are similar to basophils but are found in the connective and mucosal tissue
mast cells
PMNs refers to _____
all granulocytes
(Polymorphonuclear leukocytes)
_____ are fully mature monocytes in tissue. Are they granulocytes or agranulocytes?
Macrophages/Dendritic Cells
agranulocytes
What is the difference between a small resting lymphocytes and an activated atypical lymphocyte?
Inactive monocytes does not have very much cytoplasm when compared to the nucleus (E)
activated lymphocyte has more cytoplasm when compared to the nucleus (F)
What are the stages of granulocyte hematopoiesis?
self- renewal
proliferation stage
differentiation stage
What stage of granulocyte hematopoiesis? _______Originates from the hematopoietic stem cell (HSC). HSC are able to self-replicate (self-renew) and differentiate
self renewal
What stage of granulocyte hematopoiesis? ______ capable of cell division and differentiation
Myeloblast → promyelocyte → myelocytes
proliferation stage
What stage of granulocyte hematopoiesis? ______ capable of further maturation and differentiation, but not capable of cell division
Metamyelocyte → band → polymorphonuclear (PMN) cells
differentiation stage
______ and _____ are immature granulocytes. What stage of the granulocyte hematopoiesis?
metamyelocytes
bands
Granulocyte Hematopoiesis
polymorphonuclear cells are (mature/immature) granulocytes
mature
_____ is needed to determine morphology and will confirm presence of immature cells
Peripheral smear
______ of a WBC with diff are more reliable in pathologic states
Absolute values
How do you calculate the Absolute Neutrophil Count (ANC) if it is not given?
What type of WBC also plays a role in cytokine release and general inflammatory reponse?
Neutrophils
neutrophils progenitor matures in the marrow over ____. In a steady state, most neutrophils (will/will not) enter the bloodstream
7-10 days
will NOT!
Where is the “storage pool” of neutrophils located?
bone marrow: mature neutrophils hanging out ready to go until they get “called up”
called medullary neutrophils
Where is the “circulation pool” of neutrophils located? Where is the “marginal pool”?
About ½ circulate in blood < 24 hours before entering into the tissue to be used for up to 1-2 days in tissue
About ½ are attached to the endothelial walls: not freely floating in the blood but are mostly available if needed
What is considered neutrophilia? What are the 2 categories?
ANC greater than 7.7K
neutrophilic shift
true neutrophilia
_____ is when neutrophils from the marginal pool shift to the circulating pool. What is the timeframe? What can cause it?
Neutrophilic shift
onset within 1-2 minutes, lasts 20-30 minutes
Results from acute physical/emotional stress
exercise
seizure
paroxysmal tachycardia
epinephrine injection
post-op state
exercise
seizure
paroxysmal tachycardia
epinephrine injection
post-op state
Can all cause _____
neutrophilic shift
______ is the release of neutrophils from the storage pool (bone marrow). What will the ANC look like? What are the classifications?
True neutrophilia
ANC may be 5-6x greater than normal
spurious
primary
secondary
What type of true neutrophilia? ______ falsely elevated neutrophils (lab error)
spurious
What type of true neutrophilia? ______ increased neutrophil production by the marrow due to impaired neutrophil production regulation
primary neutrophilia
What type of true neutrophilia? _____most common; reaction to another condition, usually some sort of infection
secondary neutrophilia
Severe neutrophilia can lead to early release of ______
bands (“left shift” or “bandemia”
What do you do if you see spurious neutrophilia?
results of a lab error
wait an hour/day and repeat the labwork
What is considered mild neutropenia? Moderate? severe? agranulocytosis?
Mild neutropenia – ANC ≥1000 and <1500 cells/µL
Moderate neutropenia – ANC ≥500 and <1000 cells/µL
Severe neutropenia – ANC <500 cells/µL
Agranulocytosis - ANC <200
________ :often exacerbated by various medications. More often seen with morning specimens
Pseudoneutropenia
What is the pathophysiology of neutropenia?
Insufficient or injured bone marrow stem cells likely from marrow disease, chemo, medications, toxins or infections
shifts in neutrophils
increased destruction in the circulation
Who is neutropenia more commonly found in? What is DANC?
elderly
Duffy-null associated neutrophil count (DANC) - in patients of African descent (aka they just have a chronically low WBC)
in neutropenia ______ s/s may be absent. Why? At what ANC should you worry?
bacterial infection, no s/s because the body is not responding to the infection like it should
serious infections can occur with an ANC below 500
How does neutropenia present? What PE findings are common?
low-grade fever; skin (abscesses), ENT (otitis, sinusitis, oral sores, dental infections); pneumonia; GU infections
Severe: sudden onset malaise, prostration, fever, stomatitis, periodontitis, pharyngitis
fever
Lymphadenopathy
Signs of systemic infection (fever, tachycardia, tachypnea, hypotension)
At what point do you refer out for neutropenia?
ANC is severely low (<200 cells/µL)
ANC is persistently < 1000 cells/µL
Other signs of hematologic malignancy on peripheral smear
Presence of or progression to pancytopenia
What else would you order to work a patient up for neutropenia?
Bone marrow biopsy - evaluate granulocyte precursors and other hematopoietic stem cells; looks for other disease (infiltration, fibrosis)
(+) serum antineutrophil cytoplasmic antibodies (ANCA) - suggests autoimmune neutropenia if bone marrow is normal
(+) Rheumatoid factor and splenomegaly (via US/CT) - suggests Felty syndrome
(+) serum antineutrophil cytoplasmic antibodies (ANCA) - suggests _____ if bone marrow is normal
autoimmune neutropenia
What is the management for neutropenia?
Myeloid growth factors
Granulocyte colony-stimulating factor (G-CSF):
filgrastim (Neupogen), pegfilgrastim (Neulasta)
Granulocyte-macrophage colony stimulating factor (GM-CSF):
sargramostim (Leukine)
d/c medication that caused it
treat contributing causes (nutritional deficiencies, infections)
may be a candidate for hematopoietic cell transplatation
filgrastim (Neupogen), pegfilgrastim (Neulasta) are what kind of myeloid growth factor?
Granulocyte colony-stimulating factor (G-CSF): just neutrophils
sargramostim (Leukine) is what kind of myeloid growth factor?
Granulocyte-macrophage colony stimulating factor (GM-CSF) : neutrophils and monocytes
What is the difference between G-CSF and GM-CSF?
GM-CSF includes growth factor for neutrophils and monocytes
systemic flu-like reaction; bone pain; possible stimulation of malignancy or HIV replication; development of antibodies to growth factors
These are the SE for ______
myeloid growth factors
What is the treatment for Autoimmune neutropenia?
5 days of steroids + intermittent myeloid growth factor doses
What is the treatment for chemo-induced neutropenia?
myeloid growth factor +/- prophylactic antimicrobials
When is granulocyte infusion indicated?
indicated for bacterial infections without a clinical response to antibiotics within 24-48 hours
What is the protocol for in vs out patient therapy for neutropenic fever?
ANC >1000 cells/µL = outpatient basis
ANC 500-1000 cells/µL = management is case-based
ANC of <500 cells/µL = inpatient treatment with parenteral antibiotics
How are eosinophils distinguished on a gram stain?
Leukocytes with secretory granules in their cytoplasm that are readily stained by eosin, and which are distinguishable by a bilobed nucleus.
_____ are primarily tissue dwellers, commonly found in the spleen, lymph nodes, thymus and digestive tract
eosinophils
_____ protect the body from parasites, and play a role allergies, allergic response and asthma. What are their target organs? What is the tissue/blood ratio?
Eosinophils
skin, airway, GI tract
100:1
What are the 3 primary cytokines that are responsible for eosinophil development and differentiation?
Interleukin-5 (IL-5)
Interleukin-3 (IL-3)
granulocyte-macrophage colony-stimulating factor (GM-CSF)
What is the life span of an eosinophil?
Circulate for 8–12 hours before entering into the tissues
remain in tissue for days to weeks, average 2-5 days.
Cytokines can help eosinophils survive to 14 days or longer
What is considered mild eosinophilia? moderate/severe?
Mild - 500 to 1500 cells/µL
Moderate-Severe (Hypereosinophilia) - ≥ 1500 cells /µL
Eosinophilia can be _____ or ______.
primary or secondary
primary eosinophilia can be ____ or _____. What are they caused by?
clonal: genetic mutation or malignancy
idiopathic: when everything else has been ruled out
Which eosinophilia is more common? What is it caused by?
secondary: reactive to an underlying etiology
What is the pathophysiology behind eosinophilia?
Dysregulation of cytokines IL-3, IL-5, GM-CSF leads to an increase in eosinophil production and/or eosinophil longevity
What is the major complication with eosinophilia?
Tissue and organ damage
can happen at any eosinophil level above 500, degree of damage is NOT related to the level of eosinophils in the blood
The tissue/organ damage that does occur as a result of eosinophilia is caused by ????
Release of toxic granule products that can damage epithelial cells and nerves
Production of lipid mediators (leukotrienes, prostaglandins) which control smooth muscle contraction and recruitment of inflammatory cells
Release of cytokines which may be involved in tissue remodeling and fibrosis (causes scarring)
What are the main target organs of eosinophilia? How can you dx it?
MC target organs - skin, respiratory tract, GI tract
Biopsy of the organ will identify eosinophilic infiltration
What is the treatment for eosinophilia?
Removal of any potential causative agents
Often multidisciplinary treatment with hematology, allergist, +/- other specialists
treatment varies widely depending on the cause!
What does a basophil look like on a smear?
Leukocytes with a large quantity of dark blue-black secretory granules in their cytoplasm; the least common of the circulating WBCs.
What is the role of a basophil?
contains heparin: so helps to prevent clotting
releases histamine when in contact with allergens
IgE antibody formation, activation and hypersensitivity reactions
What is considered basophilia?
Absolute basophil count ≥ 100/µL (0.1 ×10³/µL)
Unusual, rare condition overall
What is the primary cause of basophilia?
basophilic or mast cell variants
of acute or chronic leukemia
What are some secondary causes of basophilia?
myeloproliferative disorders:
-Polycythemia vera
-Myelofibrosis
-Thrombocythemia)
Hypersensitivity or inflammatory reactions
Hypothyroidism
How would you describe a lymphocyte on a smear?
single round nucleus and receptor molecules on their surface to bind to antigens and facilitate removal of the antigenic pathogen or agent.
_____ can differentiate into plasma cells
B-cells
What is the lymphocyte class % breakdown?
T-cell - 60-80%
B-cell - 10-20%
Natural Killer Cells (NK) - 5-10 % (these are made as needed)
____ and ______ are lymphocytes that can mature and divide on demand
T cell and B cell
Where do T cells mature and differentiate?
thymus
then are exported to the blood and secondary lymphoid tissues (Lymph nodes, spleen, tonsils, MALT)
What is the function of the T cell?
destroy abnormal human cells (virus-infected, cancer) and contribute to adaptive immune response via memory T cells
What are the 3 categories of T cells?
helper T cells
Cytotoxic T cells
Regulatory T cells
types of T cells: ______ aka “CD4+ T-cell”- recognizes foreign antigens and stimulates antibody production; produces cytokines that activate other T-cells
Helper T
types of T cells: ______ aka “CD8+ T-cell” - attacks and destroys abnormal cells (i.e infected cells, cancer cells and transplanted organ cells)
Cytotoxic T cells
types of T cells: ______ - dampen or turn off the immune response of other T-cells preventing autoimmune responses
Regulatory T cells
____ and ____ can become memory cells
Helper T and cytotoxic T
Where do B cells develop?
differentiate and mature in the bone marrow, then reside in lymph tissue
What is the function of a B cell?
capture and present antigens to activate T cells, contribute to adaptive immune response via memory B cells, and contribute to humoral immunity (precursor to plasma cells). Express surface immunoglobulin (Ig) receptors
to specific antigens
______ fully differentiated lymphocyte with a
short life that produces a large number of antibodies
(Ig) until active infectious agent is removed
plasma cell
Where do NK cells mature and develop?
differentiate and mature in multiple sites:
Bone marrow, lymph nodes, thymus, liver, tonsils, uterus
What is the function of a NK cell?
first responders to abnormal human cells (virus-infected, cancer) while awaiting immune response from cytotoxic T-cells.
Can recognizes cells as “foreign” or “self”
Most healthy/normal cells express self-receptors that are recognized by the NK cells, preventing them from attacking
_____ receive signals from foreign cells. Do they require activation?
NK cells
do NOT require activation
What is considered lymphocytosis?
Absolute lymphocyte count > upper limit of normal (ULN) for age
____ and ____ are the 2 categories of lymphocytic disorders
Monoclonal
Polyclonal
What causes monoclonal lymphocytosis? Polyclonal lymphocytosis?
Benign or malignant disorder (think cancer)
Infectious
Transient
Reactive
Benign
(think reaction to something)
_____ an expanded clonal B, T, or NK cell population in the blood without any sign of infection, autoimmune process or lymphoproliferative disorder. Do NOT have any PE findings either. What does this reflect?
Monoclonal Lymphocytosis
premalignant or malignant lymphoproliferative syndrome
premalignant monoclonal B-cell lymphocytosis usually see ____ or ____ lymphocytosis. What does a low count MBL mean? High count MBL mean?
T or NK
Low-count MBL - rarely progresses to CLL
High-count MBL - more likely to become leukemia
malignant monoclonal lymphocytosis will progress to ???
Chronic Lymphocytic Leukemia (CLL)
Non-Hodgkin Lymphoma (NHL) with circulating disease
Hairy Cell Leukemia (HCL)
Large Granular Lymphocytic Leukemia (LGL)
______ is associated with underlying condition expected to normalize within 2 months after resolution of condition
Polyclonal Lymphocytosis
polyclonal lymphocystosis is most likely due to ????
MC viral infections (especially EBV), Pertussis, cat scratch disease, toxoplasmosis
emotional/physical stressor (acute illness or surgery)
drug reaction
benign persistent Polyclonal Lymphocytosis is usually due to ?????
rare, mainly in adult female smokers
Post-splenectomy
Thymoma
What is the dx workup for lymphocytosis?
Repeat CBC with diff.
Peripheral blood smear
Flow Cytometry: will detect surface antigens to specific B or T cells
What is the defines lymphocytopenia?
Absolute lymphocyte count < lower limit of normal (LLN) for age
What are some complications associated with Lymphocytopenia?
Opportunistic infections
Higher risk of malignancy and autoimmune disease
Lymphocytopenia can be ____ or _____
inherited or acquired
Name some causes of acquired lymphocytopenia
HIV and other viral infections
radiation
cytotoxic
steroids
alemtuzumab, rituximab
autoimmune disorders
zinc deficiency
chronic alcohol use
malnutrition
What does a monocyte look like on a smear?
Phagocytic leukocyte, the largest WBC, with a large ovoid (notched or kidney-shaped) nucleus and clear, grayish cytoplasm.
____ is the monocyte precursor
myeloblast
What are the functions of monocytes?
Phagocytosis
antigen presentation
inflammatory cytokine production
Monocytes allow T cell ____, _____ and ______
recognition, activation and immune response
monocytes remain in circulation for ____ before entering tissues. Upon entering tissues, what happens?
1-3 days
Upon entering tissues, differentiate into macrophages or dendritic cells
_____ of total monocyte count is stored in _____ as a reserve
Half
spleen
What is monocytosis defined as?
Absolute monocyte count > 800 cells/µL ( 0.8 x ×10³/µL )
monocytosis is usually due to a _____ that isn’t a result of hematopoietic dysfunction. What is the MC?
transient condition
bacterial infections complicated by neutropenia
What 2 medications can cause monocystosis?
steroids or colony stimulating factors
Overall, the management of leukopenia is geared toward ???? and ?????
correcting the underlying condition
prevention of complications
Overall, how do you manage leukopenia?
Broad spectrum antibiotics
Myeloid growth factors
Corticosteroid Therapy (if immune mediated)
Nutritional Therapy (if any deficits)
Splenectomy - Reserved for chronic neutropenia unresponsive to other tx
splenectomy puts you at a higher risk of ????
Complicated by risk of recurrent life-threatening bacterial infections
60x higher risk of sepsis, especially in young children
OPSI - overwhelming post-splenectomy infection (mortality 40-70% with tx)
What is a PE that you would want to avoid on pt with leukopenia?
NO rectal exams!!!
When are peripheral smears indicated?
leukocytosis, leukocytopenia
When is hypersegmentation seen on a peripheral smear?
megaloblastic anemias, sometimes with myeloproliferative disorders, or following chemotherapy (methotrexate)
When is granulation seen on peripheral smear?
seen most often with bacterial infections and in association with cytoplasmic vacuolization
When are Dohle bodies often seen on a peripheral smear? What do they look like?
Irregularly shaped blue staining area in the cytoplasm; seen with infections
_____ is a a ruptured cell remnant, classically associated with fragile lymphocytes in CLL
Smudge cell / Basket cell
An artifact of EDTA anticoagulation, this may cause the platelet count to be artifactually low. What am I?
Platelet satellitosis
Describe the process of flow cytometry. What does it detect?
A process that measures (-metry) cellular (cyto-) properties as they are moving in a fluid stream (flow), past a stationary set of laser detectors
Detects antigens or markers on the surface of the cells
Differentiates normal cells from malignant cells
What types of body products are eligible for flow cytometry?
blood, bone marrow, lymph node tissue
