Term
| Thrombocytopenia and microangiopathic hemolytic anemia (elevated indirect bilirubin+reduced serum haptoglobin) should include what conditions in the differential? |
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Definition
| Thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome (TTP-HUS) |
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Term
| Widespread hyaline thrombi formation, made up of platelet aggregates, which lodge in the microvasculature is the underlying cause of what two conditions? |
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Definition
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Term
| What is the etiology of TTP? |
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Definition
| Absence, acquired or congenital, of ADAMTS13, a metalloprotease unrelated to those involved in extracellular matrix degradation. ADAMTS13 is responsible for degrading vonWillebrand Factor. When deficient, too much vWF is present on endothelial cells, leading to platelet aggregation and formation of thrombi |
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Term
| This treatment is life-saving for TTP |
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Definition
| Plasma exchange, which replaces the deficient ADAMTS13 metalloprotease |
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Term
| Since MAHA is non-immune mediated hemolysis, what causes RBC destruction? |
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Definition
| Shear stresses imposed by obstructive thrombi in the microvasculature damage RBCs as they pass through capillaries |
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Term
| What is the most common cause of HUS? |
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Definition
| EHEC, especially O157:H7, produces a shiga-toxin that damages endothelial cells resulting in platelet aggregation, complement deficiences and drug reactions can also cause HUS |
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Term
| What is the primary distinction between DIC and TTP-HUS? |
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Definition
| DIC requires an inappropriate activation of the clotting cascade to occur, while TTP-HUS results from inappropriate platelet aggregation |
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Term
| T or F: synthesis of hemoglobin begins in the proerythroblasts and continues even into the reticulocyte stage of the RBCs |
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Definition
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Term
| Outline the steps of hemoglobin synthesis |
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Definition
| SuccinylCoA (from Krebs)+glycine->pyrrole(x4)->protoporphyrin IX+iron->heme+globin->hemoglobin chain (x4)->hemoglobin molecule |
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Term
| T or F: Hemoglobin B is the most common form of human hemoglobin |
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Definition
| False, hemoglobin A which has 2 alpha and 2 beta chains |
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Term
| The total quantity of iron in the body is: a) 4-5 grams b) 2-3 grams c)7-8 grams or d) 10-12 grams |
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Definition
| a, 4-5 grams, 65% in hemoglobin, 4% in myoglobin, 1% in heme components of CYP family proteins, .1% in serum bound to transferrin and 15-30% in storage, mainly in the reticuloendothelial system and liver parenchymal cells |
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Term
| What is the dominant storage form of iron |
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Definition
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Term
| T or F: Iron is absorbed in the distal ileum |
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Definition
| F, absorbed in the duodenum by the DMT transporter on the brush border, where it is taken up into enterocytes |
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Term
| Which enzyme facilitates the rate limiting step in heme production? |
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Definition
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Term
| Where does the rate limiting step of heme synthesis take place in the cell? |
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Definition
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Term
| T or F: After ALA leaves the mitochondrion it goes to the cytosol and condenses with another ALA to form uroporphyrinogen |
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Definition
| False, forms porphobilinogen (PBG) |
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Term
| Which intermediate in heme synthesis is water soluble and can turn up in urine in case of excess? |
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Definition
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Term
| Which intermediate in heme synthesis is excreted in feces if in excess, and which steps does it precede/succeed? |
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Definition
| coproporphyrinogen, comes before synthesis of protoporphyrinogen IX and after formation of uroporphyrinogen |
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Term
| T or F: After protoporphyrinogen IX is reduced to protoporphyrin IX, ferrous iron is inserted by ferrochelatase |
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Definition
| False, it is oxidized to protoporphyrin IX but the rest is correct |
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Term
| T or F: as the rate limiting step in heme synthesis, ALA synthase is the body's regulatory target in heme synthesis |
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Definition
| True, when more is needed it is up regulated and vice versa |
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Term
| How are the two ALA synthase genes regulated? |
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Definition
| One is expressed in all cells and responds to heme concentrations, the other is only in proerythroblasts and responds to EPO |
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Term
| Name a common cause of acquired porphyria that works by inhibiting ALA dehydratase and ferrochelatase |
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Definition
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Term
| What is the protein responsible for moving ferrous iron into the bloodstream from enterocytes? |
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Definition
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Term
| T or F: The highest sensitivity transferrin receptors are found in the liver and bone marrow |
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Definition
True, remember transferrin is the protein that transports iron in the blood
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Term
| What storage form of iron is utilized only when ferritin is unavailable? |
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Definition
| Hemosiderin, extermely insoluble and can be observed in cells indicating iron overload |
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Term
| T or F: Transferrin delivers iron directly to mitochondria for heme synthesis to take place |
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Definition
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Term
| What is the most common cause of iron deficiency anemia in men? |
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Definition
| Blood loss from a gastrointestinal bleed |
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Term
| What is the name of the inhibition target in erythroid precursor cells for low hemoglobin? |
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Definition
| Heme regulated translational inhibitor |
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