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151 Cards in this Set
- Front
- Back
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At which stage can you differentiate the 3 granulocytes?
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Myelocyte
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What is the granulocyte maturation sequence?
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Myeloblast -> promyelocyte -> myelocyte -> metamyelo -> band -> seg
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Myeloblast
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Earliest recognizable precursor cell
- prominent nucleoli - few to no granules - mitotic divisions - v. large - open chromatin pattern |
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Myelocyte
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- stage at which specific granules appear
- Azurphilic granules produce peroxidase |
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Marginating PMN's
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Located along the sides of blood vessel walls
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Dexamethasone or PGE-2
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inhibit the growth and differentiation of granulo-mono series
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Androgens
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stimulate granulocyte production
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Diff. Proliferative, Reserve and Circulating compartments
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Proliferative - cells capable of dividing (myeloblast, promyelocyte, myelocyte)
Reserve - composed mostly of banded neutrophils Circulating - PMN's with a few bands |
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Granulcyte modus operandi
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Kill microbes intracellularl or surrounding cells extracellularly via digestive enzymes such as lysozyme, lactoferrin, acid hydrolase and myeloperoxidase
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Kallikrein
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generates bradykinins that promote inflammation, vascular permeability and vasodilation. Leukocytes seek the source of this (chemotaxis)
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What is the lifespan of an average granulocyte?
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hours (min) to a few days (max)
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Metamyelocyte
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Peroxidase neg granules outnumber azurophilic granules
- this cell can no longer divide |
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What is the average size of a leukocyte (diameter)
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10-15 um
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Hypersegmentation
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Segs with greater than 5 lobes in the nucleus, seen in macrocytic, pernicious anemias or myelodysplasia
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How long does an average PMN circulate?
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6-7 hrs.
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What is the production rate of PMN's?
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1.6 billion cells per kilogram per day
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Eosinophil granules contain
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Acid phosphatase, peroxidases, proteinases. These granules are released EXTRACELLULARLY
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Eos' target...
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Fungi, protazoa, parasitic worms, large pathogens. Also involved in allergic reactions, atrophy.
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Basophil granules contain
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Histamine, leukotrienes, prostaglandins, chondroitin sulfate
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Immediate hypersensitivity reactions are associated with
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Basophils and IgE
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Reticuloendothelial system
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Composed of specialized monocytes (macrophages) located in spleen
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life span of a monocyte
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4-5 months (following a half-week long maturation and 1.5 day circ. time)
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Charactaristics of neutrophils?
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- amoeboid motility
- highly phagocytic - cytoplasmic structures penetrate the walls of venules |
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Azurophilic granules are also known as, and contain
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primary granules; peroxidase
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Secretory granules are also known as
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secondary granules
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Auer rods
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Inclusions composed of fused primary granules; almost always indicative of granulocytic leukemia
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Azurophilic granules are also known as, and contain
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primary granules; peroxidase
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Neutropenia
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<2000 neutrophils/uL. Results in increased risk of infection both from pathogenic microbes and commensal non-pathogenics that become opportunistic.
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Secretory granules are also known as
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secondary granules
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Lymphocytes that induce immunological reactions.
Primary regulators of T- and B- cell mediated responses |
Helper-inducers T-lymphs (Th)
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Cells involved in suppressing immunological reactions
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suppressor T-lymphocytes
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Cells that are involved in killing organisms with foreign antigens
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Cytotoxic T-lymphs (Tc)
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Tdh
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Delayed hypersensitivity effector cells
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Express the CD4 marker
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T helper cells
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Th1...
regulated by... |
cells that aid in the regulation of cellular immunity
IL-2 and interferon-gama (IFN-gamma) |
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Th2
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cells that aid B cells to produce certain classes of antibodies
regulated by IL-4 and IL-10 |
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Express the CD8
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T cytotoxic cells, T suppressor cells
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T suppressor cells
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suppress the T and B cell responses and express CD8 molecules
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NK cells are small granular lymphocytes (T/F)
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False
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NK cells produce these cytokines
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IL-2
IFN-gamma IFM-apha TNF-alpha |
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NK cells express this CD
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CD16
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Charactarized by recombinations of immunoglobulin H and L chain genes
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B cells
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Principal antibody is IgM
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B Cells
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Which lymphocytes come from the bone marrow and where do they reside?
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B-lymphocytes; lymphoid organs
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Lymphocytosis
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>4k/uL lymphocytes
reactive lymphs in peripheal smear |
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Primary lymphocytosis
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Accumulation of monoclonal B-cells and T-cells, immature lymphs in blood, may be transient
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Secondary lymphocytosis
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Associated with increase in absolute number of lymphocytes due to physioogic or pathologic responses to infections, toxins or cytokines
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Lymphocytopenia
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Total absolute reduction of lymphocytes <1000/uL
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MDS
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Myelodysplasia - clonal myeloid disorders by ineffective hematopoiesis, cytopenias, qualitative disorders of blood cells and their precursors - sometimes develop into AML
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What's the difference between MDS and leukemia?
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Myelodysplasia can be malignant across multiple cell lines (ie. dysfunctional platelets, leukocytes, erythrocytes, etc.) whereas leukemia is only for one cell line
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What condition is present in 85% of MDS?
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Anemia
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Pelger-Huet Anomaly
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Where mature neutrophils have an abnormally mature cytoplasm but an immature nucleus (bands and bilobed nuclei)
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What occurs to the primary granules in MDS?
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They are defective and abnormal in size and shape
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What are the clinical symptoms of MDS?
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- tiredness and fatigue (anemia)
- easy bruising (thrombocytopenia) - enlargement of spleen and liver (liver eliminating abnormal cells |
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Up to a third of MDS cases will progress into what pathology?
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Leukemia (most commonly AML)
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Refractory Anemia
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Marrow cells appear abnormal. Less than 5% myeloblasts in marrow (ie decreased production of RBC's due to marrow dysfunction)
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RARS
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Refractory anemia with ringed sideroblasts (aka sideroblastic anemia)
same as RA but with additional abnormalities in the red cell population (percipitated iron in a ring/figure8 shape) in normoblasts |
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RARS is most common in what age group?
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>50 yo
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RAEB-t
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Refractory anemia with excess blasts in transformation
Shows many features of acute myeloid leukemia - low survival rate - high chance to convert to leukemia (60%+) |
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CMML
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chronic myelomonocytic leukemia
- red cell precursors abnormal - mild reduction in plt's - |
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Secondary MDS
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MDS developed following radiation therapy or chemotherapy for other diseases
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How is MDS treated?
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GM-CSF; increases WBC in 80% of cases and other cell lines to a lesser extent; GM-CSF should not be given for CMML however
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Which cells in the granulocytic series are capable of diving by mitosis?
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Myeloblast, promyelocyte, myelocyte
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What is the earliest recognizable precursor cell in the granulocytic series?
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Myeloblast
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Granules are prominent in Myeloblasts (T/F)
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False
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At which stage do azurophilic granules become prominent?
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Promyelocyte
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What are marginating PMN's?
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PMN's that are located along side blood vessel walls and can be released into circulation when stimulated
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What hormone stimulates granulocyte production?
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Androgens
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What hormone inhibits granulocyte production?
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Dexamethasone and PGE-2
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What is the "reserve compartment" when referring to the granulocytic series?
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Banded neutrophils in the bone marrow
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Kallikrein
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Catalyzes the generation of bradykinins
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Bradykinins
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Promote inflammation by causing vasodilation, increasing permeability and increasing mucous production
CHEMOTAXIS!! also |
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Prostaglandins
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- synthesized from arachidonic acid
- vasodilation - increase in permeability - pain - induce fever |
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Peroxidase negative granules (DO/DO NOT) outnumber the azurphilic granules in Metmyelocytes?
BONUS: Metamyelocytes (DO/DO NOT) undergo mitosis? |
DO; DO NOT
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Neutrophils normally account for which percentage of WBC's in an adult?
How many (in cells/uL) are circulating in blood? |
54-75%
3000-7500 / uL |
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What enzymes are present in the granules of Eosinophils?
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acid phosphoatse, peroxidase, proteinases and arylsulfatase
Also secrete leukotrienes and prostaglandins + other various cytokines |
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Eosinophils are cells that try to kill which types of organisms?
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Fungi, protozoa, eukaryotic parasites and other large pathogens
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Basophils contain granules containing which chemicals/proteins?
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Histamine - rapid immune response
Leukotrienes and prostaglandins - promote inflammation, vasodilation, permeability and mucous production Heparin - anti-coagulant |
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Which antibody is important in immediate hypersensitivity reactions?
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IgE
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What is the least common granulocyte in the blood?
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Basophils
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What is a major charactaristic?
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Cytoplasmic vacuolization; irregular nucleus and chromatin distribution
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What is the maturation sequence (ie. tissues it resides in) of monocytes?
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4-5 days in marrow
1.5 days in blood <4 months in RES |
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What are the primary lymphoid organs?
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bone marrow and thymus
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What is the most common type of lymphocyte?
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T-Lymphocytes
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Thymocytes
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Lymphocytes located in the cortical part of the thymus lobes
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Acute Leukemias
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unregulated proliferation of WBC's with impaired maturation
Numerous immature blasts present on smear rapid onset rapidly fatal course if untreated |
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Chronic leukemias
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Unregulated proliferation of WBC's that retain some ability to partially differentiated. Few blasts and usually resemble normal mature granulocytes and lymphocytes
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What are some predisposing factors of acute leukmias?
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Chromosomal disorders such as down's syndrome
radiation, toxins |
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What are some clinical symptoms of acute leukemias?
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Fever, fatigue, weakness, weight loss and ytpically accompany acute leukemias
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Hematologic consequences of bone marrow infiltration in Acute Leukemias
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Anemia and thrombocytopenia
neutropenia (leading to bacterial or fungal infections) |
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CNS symptoms are most common in ALL (T/F)
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True; subarachnoid accumilation of leukemic cells may cause spinal cord compression
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Leukostasis
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WBC counts 100,000/uL
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What metabolic derangements result from acute leukemias?
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Hypercalcemia
Hyperkalemia Uric acid - gout, renal stones, renal failure |
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What are the clnical symptoms of chronic leukemia?
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Anorexia, fatigue, mild fever, weight loss
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In which leukemia do the blood forming cells eventally mature, differentiate but are not normal?
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Chronic leukemias
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Chronic myelogenous leukemia is also called a ______ disorder
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myeloproliferative; a disease in which marrow cells proliferate (multiply) outside of the bone marrow tissue
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What is the most common leukemia in North America and Europe?
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Chronic lymphocytic leukemia
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FAB
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French American British System - used to differentiate acute leukemias
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M0 leukemia
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undifferentiated leukemia - no signs of differentiation
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M1
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Some signs of differentiation - Auer rods
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M2
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M2 Myeloblastic leukemia: Differentiation at or beyond promyelocytes - associated with a specific change involving translocation on chromosomes 8 and 21. Has Auer rods.
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M3 or M3V
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Most cells are abnormal early granulocytes that are between myeloblasts and myelocytes.
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M4 or M4E
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Myelomonocytic leukemia - bone marrow and circulating blood have variable amounts of differentiated granulocytes and monocytes. The proportion of monocytes and promonocytes (early monocyte form) in the bone marrow is greater than 20% of all nucleated cells
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M5 (M5A and M5B)
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Monocytic leukemia
There are two form of this subtype. The first form is characterized by poorly differentiated monoblasts. M5A - all monoblasts M5B - well differentiated. usually takes flow cytometry to detect |
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M6
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Erythroleukemia (M6) - this form of leukemia is charactarized by abnormal red blood cell-forming cells, which make up over half of the nucleated cells in the marrow
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M7
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Megakaryoblastic leukemia - Blast cells look like immature megakaryocytes or lymphoblasts - distinguished by extensive fibrosis in the bone marrow. Extremely rare.
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L1
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Mature appearing lymphoblasts (T-cell or B-cells) cells are small with uniform genetic material; regular nuclear shape
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L2
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Immature and pleomorphic lymphoblasts; Cells are large and variable in size, variable genetic material, irregular nuclear shape
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L3
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Lymphoblasts (B cells Burkitt's cells) large and uniform; genetic material is finely stippled and uniform; nuclear shape is round; prominent nucleoli; cytoplasm moderately abundant
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A 66 year old woman was admitted with complaints of fatigue, malaise, and severe pain on the left side. Physical exam revealed splenomegaly and small scattered petechiae.
Lab Results: >60k WBC <50k PLT Hgb 10 g/dL 86% blasts 5% promyelocytes |
Myeloblastic Leukemia (M1)
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5 year old child was seen by her family doctor because of weakness and headaches. She had been in good health except for the usual communicable disease of childhood. Physical examination revealed a pale, listless child with multiple bruises.
Lab: 15k WBC Hgb 8 g/dL 90k PLT Segs 9% Blasts 86% |
Acute Lymphocytic Leukemia (bc it's a kid)
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55 year old male
Medical history unremarkable Presents with unexplained prolonged bleeding from a puncture wound. Also complains that gums have been bleeding and frequent prolonged epistaxis 85k WBC 35k PLT 8.5 g/dL Hgb PT = 50s, APTT = 85s, Fbgn: 25mg/dL Auer Rods |
M3 acute promyelocytic leukemia
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59-year-old female admitted for evaluation of painful swollen right lower extremity and marked leukocytosis
Physical exam revealed distended abdomen and splenomegaly; no lymphadenopathy WBC: 5k / L Hgb: 7.4 g/dL 19k PLT Diff: 6 segs, 16 lymph, 13 mono, 25 unclassified, 40 blasts |
Myelomonocytic or monocytic leukemia
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How do lymphomas differ from lymphocytic leukemias?
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Lymphomas are a group of malignant diseases with abnormal lymph node enlargement and abnormal histology. Usually there are no peripheral blood abnormalities.
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Hodgkin's disease
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Malignancy of the lymphoid tissue found in the lymph nodes, spleen, liver and marrow.
The disease spreads to adjacent lymph nodes, possibly spilling into the blood in later stages. Charactaristic: Reed-Sternberg cells |
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What are the four classifications of Hodgkin's Disease?
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Lymphocyte predominance
Nodular sclerosis Mixed cellularity Lymphocyte depletion |
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Lymphocyte predominance HD
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occurs in a nodular and diffuse variety. It typically involves high cervical lymph nodes, and nodes may be quite large.
LPHD is a B-cell proliferation |
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Nodular sclerosis HD
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stands apart from the other types by virtue of its characteristic histopathology, predilection for young females (giggity!), mediastinal orientation, and pattern of apparently contiguous spread.
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Mixed cellularity HD
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Cellular infiltrate is typified by lymphocytes, plasma cells, eosinophils and leukocytes. RS cells are usually easily found. By convention mixed cellularity is also used for cases that lack the characteristic features of other types
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Lymphocyte depletion HD
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HD occurs in diffuse fibrosis and reticular forms. Both show a striking depletion of all cellular elements. Necrosis is frequent, and the disease is often at an advanced stage at presentation with involvement of bone marrow and liver. The reticular form is characterized by numerous RS cells including pleomorphic and bizarre variants
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Non Hodgkin’s Lymphoma
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A lymphoma in which the node cellular infiltrates are generally uniformly composed of similar appearing neoplastic cells that are usually B lymphocytes
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Non Hodgkin’s Lymphoma
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A lymphoma in which the node cellular infiltrates are generally uniformly composed of similar appearing neoplastic cells that are usually B lymphocytes.
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Differentiate high grade, intermediate grade and low grade Non-Hodgkin's lymphomas
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High grade: Lymphoblastic lymphomas, small noncleaved cell, burkitt's or non-burkitt's, large cell immunoblastic
Intermediate: Diffuse large cell, follicular large cell, diffuse small cleaved cell, diffuse mixed cell Low grade: CLL Follicular small cleaved cell Follicular mixed small and large cell |
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Lymphoma stage I
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Cancer is found only in a single lymph node, in the area immediately surrounding that node, or in a single organ
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Lymphoma stage I
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Cancer is found only in a single lymph node, in the area immediately surrounding that node, or in a single organ
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Lymphoma stage II
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Cancer involves more than one lymph node area on one side of the diaphragm.
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Lymphoma stage II
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Cancer involves more than one lymph node area on one side of the diaphragm.
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Lymphoma stage III
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: The cancer involves lymph node regions above and below the diaphragm. For example, there may be swollen lymph nodes under the arm and in the abdomen.
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Lymphoma stage III
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: The cancer involves lymph node regions above and below the diaphragm. For example, there may be swollen lymph nodes under the arm and in the abdomen.
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Lymphoma stage IV
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Cancer involves one or more organs outside the lymph system or a single organ and a distant lymph node site
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Lymphoma stage IV
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Cancer involves one or more organs outside the lymph system or a single organ and a distant lymph node site
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Lymphoblastic Lymphoma
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high-grade, highly aggressive lymphomas that occur in younger individuals, typically males, and often present with an advanced stage
- originate in mediastinum, esp in boys - CNS invasion common |
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Lymphoblastic Lymphoma
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high-grade, highly aggressive lymphomas that occur in younger individuals, typically males, and often present with an advanced stage
- originate in mediastinum, esp in boys - CNS invasion common |
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Burkitt’s Lymphoma (general charactaristics)
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a B cell neoplasm characterized by small noncleaved cells that are uniform in appearance and that produce a diffuse pattern of tissue involvement
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Burkitt’s Lymphoma (general charactaristics)
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a B cell neoplasm characterized by small noncleaved cells that are uniform in appearance and that produce a diffuse pattern of tissue involvement
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Burkitt's lymphoma primary demographic
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Young boys (7yo in Africa and 11yo)
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Burkitt's lymphoma primary demographic
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Young boys (7yo in Africa and 11yo)
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(T/F) The terms small lymphocytic lymphoma and chronic lymphocytic leukemia are the same
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FALSEISH; SLL is in the lymph nodes, CLL in the blood; both are present simultaneously
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(T/F) The terms small lymphocytic lymphoma and chronic lymphocytic leukemia are the same
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FALSEISH; SLL is in the lymph nodes, CLL in the blood; both are present simultaneously
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Which lymphoma is associated with autoimmune mediated cytopenias?
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SLL/CLL
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Which lymphoma is associated with autoimmune mediated cytopenias?
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SLL/CLL
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(T/F) Follicular lymphomas are common in children
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FALSE; they are rare
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(T/F) Follicular lymphomas are common in children
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FALSE; they are rare
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Differentiate Follicular lymphomas, diffuse lymphomas?
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Follicular are almost always B-cell and usually milder, while Diffuse are B-, T- or null-cells and are more aggressive. There are no follicular high grade lymphomas.
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Charactarize monocytoid B cell lymphoma
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Medium to large cells + abundant clear cytoplasm + irregular nuclei
Frequent presence of neutrophils Association with sinuses and vascular structures |
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MALT lymphoma
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Mucosa-associated lymphoid tissue lymphoma
Extranodal: stomach, lung, salivary glands, thyroid - association with autoimmune disorders - associated with plasma cells - associated with presence of lymphoepithelial lesions |
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What bacterial organism is strongly associated with MALT lymphoma?
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Helicobacter pylori
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Hairy cell leukemia
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Mononuclear cells larger than normal lymphocytes with variable amount of cytoplasm, cytoplasmic projections, round, oval or kidney-shaped nuclei
- chromatin fine - Tartate resistant acid phosphatase (TRAP) |
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Hairy Cell Leukemia demographic
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Adults >50 years old
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Mycosis Fungoides/Sezary Syndrome
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Sézary syndrome (SS) is characterized by a malignant proliferation of CD4+ T cells, which may result in a degree of immunoparesis.
Immunosuppression is associated with an increased incidence of internal malignant neoplasms and a high rate of nonmelanoma skin cancer, particularly squamous cell carcinoma. |
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Elderly patients, usually over 50 years of age
Multiple cutaneous plaques or nodules Generalized erythroderma Late event lymphadenopathy Clinical symptoms for which disorder? |
Mycosis Fungoides/Sezary Syndrome
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