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48 Cards in this Set
- Front
- Back
Blood: basic description of amount in a person, and composition
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70cc/kg in a normal person
the only liquid organ composed of cells (erythrocytes, leukocytes, thrombocytes) and plasma (electrolytes, proteins, lipids) |
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Proteins in blood plasma and serum
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albumin, globulins (antibodies), clotting factors
serum has no fibrinogen or clotting factors |
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What are the life times of blood cells, and why are they as such?
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-short life span (except lymphocytes and macrophages)
-multiplicity of cell types -widely distributed throughout body -bone marrow must respond quickly to emergency needs for additional cells (7-8x) -stem cells must be maintained in adequate numbers throughout life, i.e. self renewal |
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Describe the maturation of red blood cells right before they leave the bone marrow.
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In the stage right before it fully matures: orthochromatic erythroblasts. They have small nuclei, which become extruded and the left over cell leaves the bone marrow into the peripheral blood stream. It is now slightly bluer than fully mature blood cells (polychromasia-- a sign of newly synthesized cells: reticulocytes)
These continue to circulate for 48 hours to make Hemoglobin to make normochromic, normocytic (normal sized) red blood cells. |
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How are polychromatic reticulocytes stained?
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Methylene blue stain which precipitates rRNA to make hemoglobin
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How many reticulocytes are made per day
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Normally are made 50-100,000 reticulocytes/ul per day
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Erythrocytes
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Anucleate, lack organelles, 5-6 x 10^6/ul, 7-8μm biconcave disc, anaerobic respiration (no mitochondria), increased Hexose monophosphate shunt (NADPH, G6PDH) for reducing oxidants (keep Fe2+ reduced), 120 day life span to travel 300 miles
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What hormone regulates RBC production? How is production of this hormone affected by anemia?
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erythropoietin, which is synthesized in the kidney, and acts on blood cell precursors in bone marrow. Erythropoietin secretion increases in anemia.
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Why is the shape of the RBC important?
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The biconcave shape increases surface to intracellular volume ratio for gas exchange
8μm RBC is deformable, to fit through 2μm capillaries. |
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Adult hemoglobin concentration, composition, and function
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12-14 gm/dL of blood
Adult Hgb A: 2 α chains, 2 β chains 4 heme molecules with iron in center Transports O2 from lungs to tissues Transports carbon dioxide from tissues to lungs |
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Describe RBC membrane
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Keeps membrane slippery, maintains electrolyte exchange, deformability
1. Lipid bilayer 2. Integral membrane proteins - ankyrin which attaches to spectrin 3. Cytoskeleton proteins - spectrin dimer |
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How do RBCs die?
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Senescent RBCs go to spleen to die: enters through a splenic artery through white pulp. Some arteries dilate into sinuses, then veins which leave the spleen; others empty out into extravascular red pulp. Plasma easily diffuses back into circulation, but RBC's need to squeeze through cords back into circulation. If not, eaten by macrophages --> extracellular hemolysis.
white pulp = lymphoid tissue red pulp = where macrophages are |
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Platelets (thrombocytes)
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Used to be called "blood dust" because they are so small.
Arise from megakaryocytes (largest cell in bone marrow). Have darker section called Granulomere: where organelles are. Have lighter section: Hyalomere. No nuclei, live for about a week, 150-400,000/ul. Contain all organelles. Contain electron dense granules. Main function of platelets: stop blooding-- primary hemostatic plug. Contain microtubules: canilucular system leading to platelet membrane. Contractile proteins to change shape (actin, mysosin). Membrane proteins: GP Ib, IIb/IIIa -- mediate adhesion |
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Megakaryocytes
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Do not undergo cellular division, only nuclear division. Fragments of the cell become platelets.
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Describe the electron dense contents of platelets and their contents
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Alpha: VWF, fibrinogen, PDGF, platelet factor 4, V, VIII
Dense bodies: serotonin Lysosomes, peroxisomes |
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platelet function
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First line of defense in hhemostasis of vessel injury
-adhesion, activation, aggregation -plasma membrane is platform for fibrin formation (clot) mediate inflammation mediate vascular constriction release of PDGF |
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Leukocytes types, percentage of each
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5-10x10^3/ul
Granulocytes: Neutrophil 55-65% Eisonophil 2-5% Basophil 1% Agranulocytes (some do have granules though): Monocyte 3-8% Lymphocyte 20-25% |
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Neutrophils
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55-65% of leukocytes
12-15u 6 hour life span in blood 1-5 day life span in tissues multilobed nucleus contractile proteins (actin, myosin) - "move, and eat" Cytoplasmic granules: specific (lysozyme, alk.phos.), and non specific |
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Neutrophil function
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Motility (contractile proteins)
-chemotaxins (released at the site of tissue damage) attract PMNs to infected or inflammed tissue Endocytosis/Phagocytosis -pseudopodiaform phagosome around organism phagosome fuse with granules H2O2 production Opsonization (antibody/complement coating) enhances phagocytes Endotoxin (in bacteria) mediates G-CSF, GM-CSF release from marrow stromal cells --> neutrophil production |
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Band neutrophil
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neutrophil with less lobed nuclei. slightly less mature neutrophils-- sign of neutrophil production
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Eisonophils
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Bilobed nucleus
Bright red granules |
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Basophils
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Granulocutes
Specific, 2ndary basophilic granules - prominent purple granules -contain heparin and histamine Receptors for IgE, when bound, degranulation and release of histamine |
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Monocyte
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Eccentric, horseshoe-shaped nucleus
Up to 20u Azurophlic granules with lysosomal enzymes Have MHC and complement receptors on surface -phagocytize antibody or complement coated cells/organism Motile and phagocytic Differentiate into tissue macrophages, living for months to years (reticuloendothelial system) |
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Lymphocytes
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8-10um
20-25% of blood leukocytes effectors of immune response T-cell: cell mediated immunity (most numerous) Can become activated --> reactive "atypical" lumphocytes B-cells: humoral immunity |
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Lifetime of granulocytes
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Less than 10 hours
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Lifetime of platelets
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7-10 days
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Site of normal blood production
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axial skeleton, sternum, skull, pelvic bone, spinal column
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Blood production progression by location
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yolk sac -> liver -> spleen -> long bones
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Bone marrow description
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microenvironment with 1) cellular matrix: support and elaboration of cytokines and growth factors: contains cells
2) ECM: scaffolding that keeps cellular material withing contact of cellular matrix fibronectin, proteoglycans, collagen hematopoietic stem cells (cellular component), fibroblasts, lymphoid progenitor, growth factors, nutrients (B12, folate, Fe), |
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Bone marrow components
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Yellow marrow (fat)
Red marrow integrating sinuses that lead to peripheral blood thin layer of endothelial cells separate precursor RBCs from peripheral circulation |
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Description of hematopoietic stem cell: properties, behavior, etc.
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Sustains hematopoiesis - generates all blood cells
Capable o self renewal throughout life High proliferative capacity: potential to give rise off millions of cells; but mitotically inactive (the actual stem cell is mostly quiescent) Pluripotent Not morphologically identifiable Extremely rare: <1 per 100,000 marrow cells Circulate in blood and cord blood |
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Hematopoietic progenitor cell
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Progeny of stem cells
No/limited self-renewal capacity Lower proliferative capacity More mitotically active than stem cells Uni- or bi-potent Not morphologically identifiable Greater in number than stem cells (1000/100,000) |
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Precursor cells
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Morphologically identifiable
Most numerous cells in bone marrow No self-renewal capacity Lower proliferative capacity than progenitor cells: 1 cell ultimately provides fewer progeny than 1 progenitor cell Unipotent: commited to 1 lineage |
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Regulation of hematopoiesis
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By hematopoietic growth factors
-glycoproteins -hormone-like: erythropoietin, thrombinpoietin Paracrine: SCF, IL's, GM-CSF |
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How are thrombopoietin levels regulated?
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Thrombopoietin made at a constant level, and is degraded by platelets
fewer platelets --> less degraded --> [thrombopoietin] increases --> more platelets synthesized |
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Myeloblast
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the most immature precursor in the granulocyte lineage: the first one that's morphologically "identifiable"-- although more needed.
Becomes pathologic in acute leukemia. Intensely basophilic cytoplasm, immature nucleus. |
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Promyelocytes
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Easily identifiable: relatively smooth unclumped chromatin in nucleus, large purple primary granules that completely cover nucleus and cytoplasm, larger than blasts.
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Myelocyte
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Pink cytoplasm develops-- secondary granules. Nucleus is more condensed. Big purple primary granules are lost. The myelocyte is the last stage that undergoes mitosis.
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metamyelocyte
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Pretty much like a myelocyte but the nucleus is more mature (indented),
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Bands
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Indentation in nucleus shape of a banded neutrophil.
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Erythroid nuclei
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Tend to be in center of cell
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Proerythroblasts
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Earliest precursor in erythrocyte lineage. Immature cell: big, intensely basophilic nucleus, unclumped chromatin. Becomes a basophilic erythroblast.
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Erythroblast
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Nucleus smaller, cytoplasm
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polychromatophilic erythroblast
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less blue, more pink cytoplasm (hemoglobin being made = pink, less RNA = blue)
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Orthochromatic erythroblast
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Small clumped nucleus that's about to be extruded, it's more blue: these are the reticulocytes that are stained blue
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Normal bone marrow aspirate
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One should see all of the stages of maturation of the different lineages
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Megakaryopoiesis
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CFU-Mega (progenitors)
Megakaryoblasts (precursors) 2N Endoreduplication (DNA replication without cell division) 16-32N Cytoplasm maturation Fragmentation of cytoplasm --> platelets Each lobe of nucleus is 2N |
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Azurophilic granules
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lysosomal = contain lysosomal enzymes
primary gr= appear first in granulopoiesis nonspecific gr = present in all granulocytes (including monocytes and lymphocytes) Specific granules - present in specific granulocytes |