問題一覧
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A. Production: Collection of all stages of erythrocytes throughout the body; the developing precursors in the bone marrow, circulating erythrocytes in the peripheral blood and vascular spaces within organs, such as the spleen
Erythron
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Erythron
Progenitors , Precursors, Immature RBCs, Mature RBCs
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Progenitors
BFU-E, CFU-E
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Erythroid Precursors
Pronormoblast, Orthochromic Normoblast
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Can be seen in the Bone Marrow
Progenitors , Precursors , Immature RBCs
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Immature RBC
Reticulocyte
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Can be seen in the Blood
Reticulocyte , Mature RBCs
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Three Erythroid Precursors Nomenclature Systems
Normoblastic , Rubriblastic , Erythroblastic
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Requirements for Growth and Maturation
Healthy Bone Marrow , EPO- Produced by Kidneys , GM-CSF, IL-3 , Other Hormones: GH, Insulin, Thyroxin, Androgens
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BFU-E --> RBC: Maturation days?
18-21 Days
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Pronormoblast --> RBC: How many days?
6 days
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In 1 BFU-E, how many RBC production?
16 RBC
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Growth Requirements
Iron, Vitamin B12, Folic Acid, Mg, Co, Zn, Vit B6, Vit D, Panthotenic Acid , Intrinsic Factor
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• Heme Synthesis • Hemoglobin
Iron
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Nuclear Maturation
Vitamin B12 Cobalamine, Folic Acid
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- Found in the parietal cells of the stomach - Vitamin B12 Absorption.
Intrinsic Factor
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- Decreased oxygen state - Detected by peritubular fibroblasts of the kidney - Low level of tissue oxygen
Hypoxia
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Oxygen sensor of the body
Kidney
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Source of EPO Production, Functions and Regulation
Kidney
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The BFU-E & CFU-E progenitors, proliferation/differentiation will turn into
Pronormoblast
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EPO Production Specific Actions: Promotes the early release of retics into the circulation (Normally it is _______, but if there is a great demand it will be shortened to 1 day = shift retics)
1-2 Days
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The reticulocyte will stay into the Bone Marrow for about _______, and after that it will be released to the blood.
1-2 Days
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No RBC Production
Anemic
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It takes how many days for Pronormoblast to be an RBC?
6 days
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Reducing the time needed for cells to mature in the bone marrow. It is called?
Accelerated Erythropoiesis
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Produced by increased erythropoietin production results from tissue hypoxia caused by such diverse factors as detective high oxygen affinity type of hemoglobin, anemia, chronic lung disease, inappropriate erythropoietin production
Secondary Polycythemia
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Common cause of secondary erythrocytosis
Smoking
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Primary cause of higher erythropoietin is?
Secondary Polycythemia
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An autosomal dominant trait that produces a defect in the regulation of erythropoietin
Familial Polycythemia
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Methods of EPO Determination: Like pregnancy test, use of lab animals
Bioassays
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Methods of EPO determination: Ag-ab reactions, monoclonal ab
Immunologic Assays
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- Aplastic Anemia - Decrease clearance of EPO - Panmyelophthesis
Increased EPO
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- Increase clearance EPO - Very high RBC count - Increase oxygen carrying capacity
Decreased EPO
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Bone marrow failure
Aplastic Anemia
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Example of Decreased EPO: Kidney Damage
Chronic Kidney Disease (CKD)
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- Normal RBC Production - Synchronous Maturation
Normoblastic Maturation
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Macrophages surrounded by developing normoblast. Macrophages salvages iron and supply it to the developing normoblast
Erythroblastic Island
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- Nurse Cells - Supplies iron to the developing pronormoblast
Macrophage
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Stage it commences - basophilic normoblast stage up to reticulocyte stage
Hemoglobinization
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Heme synthesis happens in the?
Mitochondria
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Globin synthesis happens in the?
Ribosomes
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Pyknosis and nuclear extrusion giving rise to reticulocyte
Orthochromatic Stage
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Erythrocytes Maturation: Release in the circulation - retics - after _____
1-2 days
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- Abnormal Maturation - Asynchronous Maturation
Megaloblastic Maturation
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Nuclear maturation lags behind cytoplasmic maturation
Asynchronous Maturation
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Causes: Vit B12 deficiency, Folic Acid Deficiency, Malabsorption, Lack of IF, Infection
Megaloblastic Maturation
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Essential requirement for nuclear development:
Vitamin B12 deficiency , Folic Acid Deficiency
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Problems affecting Vitamin B12 Absorption
Malabsorption , Lack of IF, Infection
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Bacteria that can cause stomach ulcer
Helicobacter Pylori
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Fish Tapeworm Infection, Parasitic
D. Latum
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Abnormally large pronormoblast
Megaloblast
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Nuclear Fragmentation
Karyorrhexis
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Abnormally large blood cells
Macrocyte
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- Abnormal RBC - Inclusion composed of DNA
Howell Jolly bodies
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Blood Structure and Function:
Diameter: 6-8 um
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Erythrocyte Structure: 1/3 of the cell diameter
Central Pallor
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Primary function is to transport O2 from lungs to tissues
Red Blood Cells
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- RBC Membranes Proteins: Lipids: Carbohydrates:
50%, 40%, 10%
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- Transport substances - Links lipids membrane to cytoskeletal proteins - Transport sites, adhesion site, signaling receptors - Ankyrin complex
Transmembrane/Integral Proteins
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Ankyrin Complex:
Band 3, Glut 1, Glycopherin A (Sialic Acid), Protein
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Anion transport
Band 3
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Glucose Transport
Glut 1
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- Sialic Acid - Zeta Potential (negative charge)
Glycopherin A
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Ratio of Protein
4:1
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Main cytoskeletal proteins:
Spectrin
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Two types of Spectrin:
Alpha Spectrin , Beta Spectrin
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Shape and Flexibility - Actin Junction Complex
Cytoskeletal/Peripheral Proteins
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Provides membrane structural integrity
Actin Junctional Complex
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Maintaining the horizontal & ventral structure of RBC
Band 3, Protein 4.1, 4.2 , Spectrin, Actin
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40% Lipids is composed of
Phospholipid Bilayer
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Phospholipid outer layer:
Phosphatidyl/Choline & Sphingomyelin
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Phospholipid inner layer:
Phosphatidyl/Serine & Phosphatidyl Ethaholamine
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Selective entry of substances into RBCs
RBC Permeability
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Does not allow Na, K, Ca to enter the RBC
Impermeable
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It allows water, bicarbonate and chloride to enter the RBC
Permeable
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In ATP dependent cation pumps, it has two defect
Cell Swelling, Cell Shrinkage
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Maintains the RBC intracellular & extracellular cation
Na-K AtPase
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In RBC Intracellular and Extracellular Cation, the Primary IC of Potassium has a ratio of?
25:1
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In RBC Intracellular and Extracellular Cation, the Primary EC of Sodium has a ratio of?
1:12
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Metabolic Pathway
Embden-Meyerhof Pathway (EMP), Hexose Monosphate Shunt (HMS) / Penrose Phosphate Pathway (PPP), Luebering-Kapoport Pathway (LKP), Methemoglobin Reductase Pathway (MRP)
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In this type of pathway the RBC lacks mitochondria and nucleus. It contains hemoglobin only.
Embden-Meyerhof Pathway
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- Anaerobic Glycolysis - Produce 2 mol of ATP - A source of ATP Requirement which composed of 90-95% - Support three metabolic pathways
Embden-Meyerhof Pathway
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- Cell rigidity and decrease survival - Affecting shape and flexibility of RBC it became rigid
Lower level of ATP
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The plasma glucose
Glycolysis
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Maintain cell membrane structure and intracellular substances
ATP
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5-10% of energy requirement
Hexose Monosphate Shunt
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In Hexose Monosphate Shunt, what is the oxidize form of glutathione
GSSG
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In Hexose Monosphate Shunt, what is the reduced form of glutathione?
GSH
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Prevents hemoglobin denaturation
GSH
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To protect and preserve hemoglobin you need to reduced the?
GSH
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Abnormal RBC inclusion composed by hemoglobin
Heinz Bodies
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During megaloblastic maturation we have what type of DNA?
Howell Jolly Bodies
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Product of Emden-Meyerhof Pathway?
ATP
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Product of Hexose Monophosphate Pathway
GSH
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Produce: 2,3 DPG - regulate hemoglobin affinity to O2
Luebering-Kapoport Pathway
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The role of this pathway is to make sure that the iron will remain in ferrous state by preventing the oxidation of ferrous iron to ferric iron
Methemoglobin Reductase Pathway
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The iron is in the what type of state? Which is functional and capable of transporting oxygen.
Fe2+ (Ferrous State)
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The hemoglobin's iron is in the what type of state? If the hemoglobin is non-functional and incapable of transporting oxygen.
Fe3+ (Ferric State)
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The methemoglobin reductase is also called?
Cytochrome B5 Reductase
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Mechanism of RBC Production
Fragmentation , Osmotic Lysis , Erythrophagocytosis , Splenic Spitting, Splenic Culling, Complement , Hgb Denaturation