Term
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Definition
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Term
| What are the different stages of blood development? |
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Definition
Primordial (Yolk sac): Week 3 of gestation
Liver, Spleen, Thymus: 5 weeks - 5 months
Bone marrow: 5 months - life |
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Term
| Where do the different proteins present in the blood come from? |
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Definition
Liver makes most plasma proteins
B-lymphocytes make immunoglobulins
Endothelial cells, megakaryocytes make VWF |
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Term
| What are the basics behind the derivation of blood from germ layers in embryology? |
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Definition
Blood is a connective tissue, derived from extraembryonic mesoderm
Angioblasts within the yolk sac differentiate into blood islands and endothelium
The yolk sac produces primitive erythroblasts (larger, nucleated, with embryonic hemoglobin) |
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Term
| Where are the different blood cells produced during hematopoeisis? |
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Definition
Liver: produces granulocytes, platelets, and definitive erythroblasts (nucleated red cells)
Spleen: produces mostly erythrocytes
Thymus: produces lymphocytes (T-cells)
Bone marrow: @ 2-3 months, medullary tissue first develops in the clavicle. By 5 months, all blood cell types are produced
Lymph nodes: produce lymphocytes and RBCs from 5 months until birth |
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Term
| What is the basic structure of bone marrow? |
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Definition
Bone marrow is in the medullary cavity of long and flat bones
Red marrow is active in hematopoiesis
Yellow marrow has been replaced by fat
Stroma is the connective tissue
Hematopoietic cords are blood forming cells
Sinusoids are capillaries that serve as the point of entry into circulation |
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Term
| What are the functions of bone marrow? |
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Definition
Site of hematopoiesis
Part of reticulo-endothelial system (RES which includes all macrophages)
-Macrophages destroy old cells
-Recycles cell components, e.g. proteins, iron
Hemoglobin breakdown
Porphyrin -> Bilirubin -> excreted in bile -> stool
Iron
-Transported bound to transferrin
-Stored in ferritin, hemosiderin
-Recycled back into new hemoglobin |
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Term
| What are colony forming cells? |
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Definition
| Cells that will give rise to a colony (group) of hematopoietic cells a.k.a. colony-forming units (CFUs) |
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Term
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Definition
| Growth factors made by endothelial cells and fibroblasts of the bone marrow stroma, T-lymphocytes, and macrophages |
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Term
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Definition
They are the earliest recognizable lineage-specific precursors
Large size
Large nucleus, sometimes with nucleoli
Blue cytoplasm (lots of protein synthesis)
erythroblasts
Myeloid (granulocytic): myeloblasts
lymphoblasts
Platelets: Megakaryoblasts |
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Term
| What is the problem with using the H&E stain to identify bone marrow cells? |
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Definition
Many bone marrow precursor cells look similar using the stain
They have to be stained for antigens specific to each cell type for identification |
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Term
| What is the basic lineage of all blood cells? |
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Definition
Pluripotent Stem Cells(undifferentiated, self-renewing)
then
Committed lineage-specific precursors (self-renewing)
then
Differentiated blood cells (incapable of replication) |
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Term
| What does the pluripotent blood stem cell lead to? |
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Definition
Multipotent Stem Cell
-Granulocytes
-Macrophage/Monocytes
-Erythrocytes
-Megakaryocytes which lead to platelets
Pre-B Cell
Pre-T Cell |
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Term
| What are some growth factors involved in hematopoeisis? |
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Definition
Stem cell factor (SCF) for pluripotent stem cells
Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF)
G-CSF (Granulocyte Colony Stimulating Factor)
M-CSF (Monocyte Colony Stimulating Factor)
Interleukin-5 for eosinophils
Thrombopoeitin and GM-CSF for Megakaryocytes (CFU-Meg)
Erythropoietin, GM-CSF, IL-3, SCF for BFU-E (Blast forming units-Erythroid) |
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Term
| What are some growth factors that are used clinically? |
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Definition
Erythropoietin: used for increasing hematocrit in people with renal failure, HIV
G-CSF: used to increase neutrophils in people receiving chemotherapy
Thrombopoeitin: used to increase platelets in people receiving chemotherapy
Early growth factors are not used clinically yet because they tend to have more effects on the vascular system, potentially causing capillary permeability and fluid leak |
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Term
| What is the sequence of erythrocyte creation? |
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Definition
Proerythroblast - looks like a much bigger lymphocyte
Basophilic erythroblast - smaller nucleus, blue cytoplasm
Polychromatophilic erythroblast - smaller, darker nucleus, blue-gray cytoplasm
Orthochromic normoblast - very small, dark nucleus, gray-orange cytoplasm
Reticulocyte - NO nucleus, slightly gray-blue tinged cytoplasm
Mature erythrocyte - NO nucleus, pink bi-concave disk |
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Term
| What are examples of abnormal erythropoiesis? |
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Definition
Abnormal hemoglobin production
-Thalassemias (Beta-thalassemia caused by a splice site mutation)
-Sideroblastic anemia where there are ringed sideroblasts (sideroblasts have iron-containg mitochondira)
Abnormal nuclear development
-Megaloblastic anemia (B12 and folic acid deficiencies)
Absent erythropoeisis or red cell aplasia
May be acquired or congenital |
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Term
| What is the sequence of myelopoeisis? |
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Definition
Myeloblast
Large nucleus, medium blue cytoplasm
Promyelocyte
Larger cell size, cytoplasm may be lighter blue
Primary granules (small, red) overlie the nucleus
Myelocyte
Nucleus becomes smaller, cytoplasm becomes pink-salmon
Specific granules develop
Metamyelocyte
Nucleus becomes indented (kidney bean)
Cytoplasm is pink-salmon, specific granules present
Band form
U-shaped nucleus
Cytoplasm is pink-salmon, specific granules present
Mature granulocyte - Neutrophil, eosinophil, or basophil |
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Term
| What abnormalities of myelopoeisis |
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Definition
Abnormalities of nuclei
Megaloblastic anemia can also affect myeloid development: very large band forms
-hypersegmented neutrophils
Absent myelopoiesis
-Acquired or congenital neutropenia
Excess promyelocytes (leukemia) |
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Term
| What is the sequence of monocyte development? |
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Definition
Monoblast
Indistinguishable visually from other myeloblasts
Promonocyte
larger than monocyte, may have folded nucleus
Monocyte/Macrophage (aka Histiocyte)
may contain undigested storage material
(organisms, iron, lipids, carbohydrate, etc.) |
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Term
| What are some macrophage abnormalities? |
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Definition
Storage diseases
Macrophages may be large and filled with undigested material due to lysosomal enzyme deficiencies
ex: Gaucher’s disease
-Glucocerebrosidase deficiency
-Causes enlargement of spleen, liver, and brain damage
other ex's - Cystinosis (crystals), Niemann-Pick disease (lipid storage disorder), iron overload, hemophagocytosis (ingesting other blood cells) |
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Term
| What is the sequence of lymphopoiesis? |
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Definition
Lymphoblasts
large size, large nucleus
small amount of blue cytoplasm -
(High nuclear:cytoplasmic ratio)
Lymphocytes
smaller, denser nucleus
sometimes more cytoplasm |
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Term
| What are some abnormalities of lymphopoeisis? |
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Definition
Absent B- or T-lineage cells
-Causes immunodeficiency
-Congenital (B, T, or combined)
- Acquired - Acquired Immunodeficiency Syndrome (AIDS) from HIV-1 infection
Abnormal or excess growth of lymphoid cells (lymphoma) |
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Term
| What is the sequence of megakarypoiesis? |
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Definition
Megakaryoblast
looks like lymphoblast
Megakaryocyte
very large cells with multi-segmented nucleus (16-64n)
Platelets
cytoplasmic buds from megakaryocytes
(Demarcation membrane subdivides cytoplasm) |
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Term
| What are some abnormalities of megakaryopoeisis? |
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Definition
Absent megakaryocytes
-Congenital
Increased production
-Platelets destruction, ex. immune-mediated thrombocytopenia
-Myeloproliferative disorder: essential thrombocytosis |
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Term
| What is abnormalities of hematopoeisis? |
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Definition
Deficient : Bone marrow failure
Disordered: Myelodysplastic syndrome
Excessive
-Myeloproliferative disorders (“pre-leukemias”)
-Leukemias |
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Term
| What can happen in bone marrow failure? |
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Definition
Absent or deficient hematopoiesis
Deficiency of only one cell type (cytopenia)
-Red cell aplasia
-Neutropenia
-Thrombocytopenia
Deficiency of all cell types = aplastic anemia
Can be congenital or acquired from
Misdirected antibody production (autoimmune)
Toxic effects of chemicals, medications
Viral infections |
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Term
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Definition
absent hematopoiesis involving all cell types
-inherent abnormality or toxic effect on stem cells
-immunologic destruction of stem cells
-abnormal bone marrow microenvironment
may be treated by immunosuppression, growth factors, or bone marrow transplantation
high rate of mortality w/o BMT |
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Term
| What can happen in abnormal erythropoeisis? |
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Definition
It results in anemia
Symptoms - tiredness, palor
treatments - RBC transfusion, erythropoeitin |
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Term
| What can happen in abnormal myelopoiesis? |
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Definition
Results in neutropenia
symptoms - bacterial, fungal infections
treatments - antimicrobial, G-CSF |
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Term
| What can be a cause of increased (abnormal) megakaryopoeisis? |
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Definition
Thrombocytopenia is immune-mediated platelet destruction. This increases megakaryopoeisis
symptoms - bleeding
treatments - platelet transfusions, thrombopoietin |
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Term
| What is fanconi's anemia? |
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Definition
Aplastic anemia
Predisposition to acute myeloid leukemia
Short stature
Limb abnormalities
-small thumbs
-radial hypoplasia
Genitourinary anomalies
Abnormalities of skin pigmentation (different skin color than rest of family)
remember looks Adopted = Aplastic Anemia |
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Term
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Definition
Excessive hematopoieis
Any of the blood cells may be produced in abnormally large numbers, due to loss of growth regulation
Dysregulation is often due to genetic mutations due to translocation of oncogenes
Blood cell malignancies are called leukemias
Single cell type, or mixed (stem cell abnormality)
Leukemias cause death by tissue infiltration and impairing the functions of normal organs
Malignant cells from other organs can also metastasize to the bone marrow |
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Term
| What are some examples of leukemias? |
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Definition
Lymphoid leukemia
Myeloid leukemia (granules and Auer rods)
Chronic myelogenous leukemia (increased numbers of all types of myeloid cells) |
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