Term
| List the hereditary membrane disorders involved with erythrocyte skeletal protein abnormalities. |
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Definition
| Hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis, and hereditary stomatocytosis syndromes |
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Term
| List the hereditary erythrocyte membrane disorders involved with abnormal membrane permeability |
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Definition
| Acanthocytosis, and paroxysmal nocturnal hemoglobinuria |
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Term
| Pathophysiology of hereditary spherocytosis |
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Definition
| hemolysis, RBCs are deficient in functional spectrin (cells are too permeable to Na+ ), disorder of vertical protein interactions (due to deficiency in spectrin and ankyrin, defects in spectrin and ankyrin (uncoupling of inner and outer lipid bilayer), membrane loss (decreased surface area to volume ratio and reduced flexibility), other membrane abnormalities (decreased membrane lipids and influx of Na+), and destruction of spherocytes in spleen (low glucose, not enough ATP to pump out excess Na+) |
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Term
| Pathophysiology of hereditary pyropoikilocytosis |
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Definition
| defects in horizontal membrane protein interactions due to inherited defects (defect in α spectrin, mutation), defects cause disruption of membrane skeletal lattice, cell destabilization and cell fragmentation (poikilocytes) |
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Term
| Laboratory findings associated with hereditary spherocytosis |
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Definition
| decreased hemoglobin (> 10g/dL), high reticulocyte count (>8%) |
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Term
| Peripheral blood smear associated with hereditary spherocytosis |
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Definition
| shows spherocytes, retics and nRBCs in normal shape, polychromasia |
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Term
| RBC indices associated with hereditary spherocytosis |
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Definition
| normal MCV (77-87 fl), MCH but increased MCHC ( >36 g/dL) |
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Term
| bone marrow associated with hereditary spherocytosis |
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Definition
| normoblastic erythroid hyperplasia (increased erythropoiesis) |
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Term
| osmotic fragility associated with hereditary spherocytosis |
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Definition
| increased (more resistant to lysis) |
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Term
| Laboratory findings associated with hereditary pyropoikilocytosis |
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Definition
| hemolytic anemia yields hyperbilirubinemia (bilirubin in urine), serologic studies for hemolytic disease of the Newborn are negative, positive thermal sensitivity test (fragments at 46°C) |
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Term
| Peripheral blood smear associated with hereditary pyropoikilocytosis |
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Definition
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Term
| RBC indices associated with hereditary pyropoikilocytosis |
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Definition
| very low MCV due to RBC fragments |
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Term
| osmotic fragility associated with hereditary pyropoikilocytosis |
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Definition
| increased osmotic fragility |
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Term
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Definition
| measures the RBCs resistance to osmotic stress by placing them in varying concentrations of NaCl. As the tonicity decreases the cellular ionic gradient increases and fluid moves into the cell, normal cells resist lysis down to 0.5% NaCl |
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Term
| Increased osmotic fragility |
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Definition
| means that the membranes of the RBCs are more fragile and lysis begins at a higher concentration of NaCl, typical of spherocytes |
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Term
| Decreased osmotic fragility |
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Definition
| means that the membranes of the RBCs are less fragile and lysis begins at lower concentrations of NaCl, typical of thalassemia |
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Term
| Etiology of Paroxysmal nocturnal hemoglobinuria |
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Definition
| uncommon acquires disorder of RBC membrane in that RBCs are abnormally sensitive to lysis by complement due to absence of antigen |
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Term
| Pathophysiology of paroxysmal nocturnal hemoglobinuria |
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Definition
| stem cell somatic mutation (abnormal clone of differentiated hematopoietic cells which binds abnormally with lots of complement and causes lysis), deficient in regulation of complement system (CD55 and CD59 and glycolipid which connects those receptors to the cell deficient on RBCs), pancytopenia and usually develops leukemia |
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Term
| Laboratory findings associated with paroxysmal nocturnal hemoglobinuria |
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Definition
| severe anemia due to decreased hemoglobin (8-10 g/dL), normocytic normochromic, high retic count (5-10%), nRBCs, hemosiderinuria (hemosiderin in RBCs), immunophenotyping shows three different cells (CD5, CD59 and CD4) via fluorochrome that binds to the glycoprotein lipid |
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Term
| Bone marrow associated with paroxysmal nocturnal hemoglobinuria |
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Definition
| normoblastic hyperplasia or hypocellular |
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Term
| Vertical protein interaction defects |
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Definition
| are associated with abnormal interactions between the skeletal lattice and integral membrane proteins. Defects cause uncoupling of the lipid bilayer |
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Term
| Horizontal protein interaction defects |
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Definition
| are associated with mechanical stability. Defects cause disruption of skeletal lattice, membrane destabilization, cell fragmentation and poikilocytes. |
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Term
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Definition
| are membrane receptors to inhibit complement accumulation on the RBC. In PNH, these receptors are absent because the glycoprotein which anchors them to the cell membrane are absent. Their absence causes accumulation of complement on the RBC which causes them to lyse. |
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Term
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Definition
| detects three types of cells (type I, type II and type III) via binding of fluorochrome to the glycoprotein anchor. Immunophenotyping will detect CD 59 (MIRL) and CD 55 (DAF) due to the presence of their glycoprotein anchor in normal patients. But in people with PNH these cells will be absent |
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Term
| Vertical defects are characteristic of disorders |
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Definition
| in which there is spherocytes and hemolysis of the RBCs due to selective loss of portions of the bilayer, loss of cell membrane, and decreased surface to area volume ration. These diseases are due to uncoupling of the lipid bilayer. Examples of vertical disorders are hereditary spherocytosis, hereditary elliptocytosis, hereditary stomatocytosis, acanthocytosis, and PNH |
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Term
| Horizontal defects are characteristic of disorders i |
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Definition
| in which there is RBC fragmentation because the membrane is destabilized because the skeletal lattice is disrupted. Examples of horizontal disorders are hereditary pyropoikilocytosis |
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