Module 3 hematology 4057
A nucleated RBC iron is called ?
sideroblast
Giant platelets
size of RBC or larger
Common sites for BM samples
- Adult and children: posterial superior iliac crest, sternum, and anterior superior iliac crest, flat bone - Newborn: Upper end of the tibial bone
B lymphocytes
- B lymphocyte precursors arise in BM from CLP derived from HSCs - Undergo ag-independent phase of development in BM. - Exit as virgin or naive B lymphocutes - 15-30% of PB lymphocytes -Marker: CD 10,19,20,21,22,24,38 - Present ag to T cell - Precursors of Ig-secreting plasma cells - Program to make a specific ab targeted against specific ag by rearranging its immunoglobulin genes
progenitor cells of platelet
- BFU - MK - stem cell - Then CFU - MK - progenitor cells - Cytokines primarily responsible for regulation: IL-3, GM-CSH, SCF
TPO mode of action
- Binds to circulating platelets, marrow MKs - Is internalized and degraded when bound to plts - When plts increases --> free TPO is decreased to bind MK precursor cells in the marrow --> stimulation of BM production is decreased.
sinus/sinusoid
- Capillary that consists of an endothelial lining with a basal lamina and adventitial cells that cover up to 60% of outer surface - Cell pass through by crossing between adventitial cells, basal lamina, and space between endothelial lining cells
core biopsy
- Cellularity ( ratio of cells and fat). Focal rather than diffuse problems. perform when dry tap is experience - Procedure: insert cutting blades into cannula, cut medullary bone, withdraw blade into cannula, withdraw all form patient - stains: Hematoxylin and eosin (H&E), Giemsa, Prussian blue.
Platelet clumping
- Due to autoantibody cross reacting abs with EDTA lead to falsely low count
lymphopoiesis
- Effector T cells responsible for cell-mediated cytotoxic reactions - Provide helper activity for B cells, macrophages, and helper T cells - Suppress other t-cell immune responses.
low power examination
- Evaluate marrow cellularity, cell to fat ratio
immunoglobulins
- Five types of heavy chains: A, D,E,G,M - Two light chains: kappa and lambda
T lymphocytes
- Form in the thymus and other lymphatic tissue and attack cancer cells, viruses, and foreign substances - T lymphocytes have receptors for Fc portion of IgG (CD16) - Markers: CD2,3,5,7,25,4,&8 - Stages: Pro-T cell, Pre-T cell, double positive, single positive, thymocyte, and T cells CD4 - T helper CD8 - t cytotoxin
central vein
- Formed from the capillary sinusoid and leads to the systemic circulation
Basophils
- Function: same as mast cells. mediators of inflammatory responses, especially hypersensitivity reaction such as asthma, urticaria, allergic, rhinitis, and anaphylaxis. - Large, heavily staining water soluble granules (heparin and histamine) - Irregular shaped cytoplasm, and nucleus - Markers: CD40L
Megakaryocytes location
- Lie over the endothelial apertures in sinus walls and discharhe platelets into the lumen of the sinus.
antigen- independent lymphopoiesis
- Location: lymphoid tissue, begin with CLP cell, results in immunocompetent T and B lymphocytes ( not yet reacted with ag) migrating to secondary lymphoid tissue
Thrombopoietin (TPO)
- Major humoral factor regulating platelet development, influences all stages of MK production. - Stimulates progenitor cell mitosis, maturing cell endocytosis, maturation and platelet release in a process of demarcation. - Production primarily by liver, kidney, spleen, BM - Produce at the constant rate. - MK nucleus remains in marrow after platelets release. the Nucleus is then get engulfed by marrow macrophages. - Survial: 9-12 days - 2/3 are release, and 1/3 remain in spleen.
If a neutrophil lacked the ability to produce L-selectin, which of its functions or abilities would be disrupted
- Margination
Megakaryocytopoesis
- Mitosis - Endomitosis: doubling DNA content without nuclear division (Karyokinesis) or cell division (cytokinesis) - Increase in cell size with maturation stage - Nucleus goes from round to bilobed to multilobed - Diffuse granulation delineated by demarcation zone
Endomitosis of platelet
- Mks become polyploid - DNA content of 8N->128N - Increased DNA content within a single highly lobulated nucleus.
erythropoietic island
- Near sinuses - a single macrophages surrounded by erythroblasts in varying stages of maturation - macrophages provides source of iron (hemosiderin), also phagocytizing rejected RBC.
Monocytes
- Orders: CFU-GEMM --> GFU - M --> Monoblast --> pro-monocyte --> Monocyte - Granules contain >50 secretory compounds - Largest cell in peripheral blood -Markers: CD11b/CD18, CD13, CD14, CD15 -Function: same as macrophages. Activate innate and adaptive Immune response, Ingest and kill microorganisms, inhibit growth of intracellular microorganisms, activate T lymph. , killing is nonspecific. activated by endotoxins and naturally occurring opsonin, bind direct to surface of microorganism and release cytotoxin, remove toxic from blood, and phagocytize cellular debris, aging cells to conserve iron, acting as ag presenting cells, produce cytokins, stimulate proliferation and differentiation of lymphocytes through cytokines secretion. -Major role: initiating and regulating the adaptive Immune response (host defense), and eruthrophagocytosis Macrophages in other organs: Kupffer, alveolar, microglial, Macrophages have faster response than neutrophils
Bone Marrow Evaluation
- RBC disorders like anemias, erythrocytosis and polycythemias that can't be diagnosis by routine lab tests - WBCs disorders like leukopenia, and unexplained leukocytosis - Abnormal cells, and immature cells in peripheral blood - Platelet disorders such as thrombocytopenia. - Systemic disease: possible metastasis of solid tumors from elsewhere in the body, fever of unknown origin from fungal and parasitic infection, hereditary or acquired diseases that involve bone marrow histiocytes, or to monitor therapy.
Platelet production
- Stage I: megakaryoblast - scant basophilic cytoplasm, no visible granules, round nucleus, visible nucleoli - Stage II: promegakyaryocyte - increased cytoplasm, primary basophilic. Few visible azurophilic cytoplasmic granules. Indented or bilobed nucleus, beginning of demarcation membranes. - Stage III: Granular megakaryocyte - numerous cytoplasmic granules, abundant acidophilic cytoplasm, large, multilobed nucleus. no visible nucleoli - Stage IV: Mature megakaryocyte - abundant acidophilic, very granular cytoplasm. demarcation zones present. multilobulated nucleus. no visible nucleoli. - 2N ->4N in early stage - 8n-32N in maturation stage - release by marrow sinus to platelets
Lymphocytes
- T, B, and Nature killer cells - humoral immunity, and cell-mediated immunity - Function: recognize and react with specific antigens, work with macrophages to eliminate pathogens, provide long-lasting immunity to previously encountered pathogen -Life span: several years or die within hrs or days - T-lymphocyte: cell-mediated immunity, required interaction with macrophages, three functional subsets: T helper, T cytotoxin, and T regulatory. - B lymphocyte: primary effector for humoral immunity, production of antibodies in plasma cells. - NK cells: effector cells of innate immunity
Aspirate Bone marrow
- determine types of cells and relative proportion of each and cellularity - procedure: shave and clean site, inject anesthetic, cut site, penetrate skin with needle, attach syringe, aspirate bone marrow quickly to prevent clotting
Megakaryocytic hypoplasia
- less than 2 megas/field
An individual who has a mutation in the CD18 gene that results in absence of the beta2-intergrin on the leukocyte membrane will likely have
- life-threatening bacterial infections
The following cells are found in the granulocytic proliferating pool (mitotic pool) of the marrow:
- myeloblasts, promyelocytes, and myelocytes
antigen- dependent lymphopoiesis
-Begin with recognition of and interaction with antigens _specific antigen receptors on surface of immunocompetent B and T lymphocytes - Result in formation of effector T and B lymphocyte - Mediates adaptive immune response.
What crystal proteins play a role in the cytotoxic and proinflamatory properties of eosinophils
Charcots-Leyden
Lymphocytes location
Cluster around small artery
Neutrophil extracellular traps (NETs) use what two substances to ensnare and kill microorganisms?
DNA and granule contents
Iron stored in marrow?
Hemosiderin - Stains brownish-blue with Wrights stain. To veryfu iron, a Prussian blue stain is used and the iron appears as blue staining granules
Basophils and mast cells have receptors for which immunoglobulin?
IgE
Segmented neutrophils are more capable or egressing from the bone marrow into the peripheral blood than myelocytes because
Mature neutrophils more easily deform through the small pore diameter to endothelial cells of the marrow sinusoids
platelet satellitism
Platelet adhere to neutrophils and some other WBCs in EDTA. - Non specific abs in the presence of EDTA - False low platelet count.
Primary granules first appear in the
Promyelocyte
A patient was seen in the ER for symptoms of appendicitis. A complete blood count was ordered/ The WBC count was 20X10^3/mcL and the segmented neutrophil 60%, 15% band neutrophil, and 20% lymphocytes. All other parameter were within the reference range. there results are most likely due to
Release of neutrophil from the bone marrow maturation/post mitotic compartment
An absolute neutrophilia is most likely to be associated with
bacterial infection
Megakaryocytic hyperplasia
clusters of megakarocytes or promegakaryocytes are seen in every field - Hyperplasia: enlarge cells and over reproduce
NK cells
cytotoxin lymphocytes - Function: part of innate immune system, key role in cytolysis of both tumor cells and pathogen-infected cells
Hemopoietic cords
developing blood cells
Eosinophil
eosinophil granules are the primary source of cytotoxin and pro-inflammatory properties of the eosinophil - Associated with allergic diseases, parasitic infection, and chronic inflammation - Major role: defense against helminth, parasites via a complex interaction of eosinophils, the adaptive immune system and the parasite Marker: cd9, cd11a, CD11b, CD11 c, CD13
High power examination
evaluation of morphology, differential count, M:E ratio - M:E ration in adult is 1.5:1 or 3.3:1
Neutrophils
found in: BM, PB, marginating PB, tissue - Three pools: mitotic pool, maturation pool, storage pool. - Same precursor as eosinophil and basophil. Differentiate at myelocyte Order:CFU-GEMM -> CFU-GM --> Myeloblast --> promyelocyte --> neutrophilic myelocyte .--> metamyelocyte --> band neutrophil -> segmented neutrophils - CD marker: CD13,33,38 Function: adhesion and migration to tissue, phagocytosis - 2nd granule begin at myelocyte
The average cell turnover rate for granulocytes and monocytes in the peripheral blood is?
hours
Iron stored in erythropoietic cords and deliver to the red cell precursors is?
hystiocyte
Leukocyte migration to the tissues is regulated by leukocyte-endothelial cell recognition that requires:
interaction of adhesion molecules and their receptors
Granulocytes location
lie away from the sinuses and close to trabeculae (sponge bone)
An ___ has cytoplasm with a ground glass appearance while a ___ contains cytoplasm r=that is pinkish to clear in color
monocyte, neutrophil
Erythroblasts location
near sinuses
Monocytes function in the immune response by their ability to ___ and function in the adaptive immune response by ___ and ___
phagocytose; antigen presentation; cytokine secretion
Which of the following leukocytes are most likely to resemble the morphology of a monocyte?
reactive lymphocyte
The hallmark of differentiating myelocytes from promyelocytes morphologically is the visual identification of what in the myelocytes?
secondary granules
