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73 Cards in this Set
- Front
- Back
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What is hematocrit?
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ratio of red cells to total blood volume
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In a patient with a chronic blood loss anemia, what do we see to compensate?
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fluid shifts from interstitial fluid to blood vessels to retain volume; hematocrit now drops; erythropoietin/reticulocyte increase
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Why might patents with hemolytic anemia benefit from splenectomy?
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most RBC damage occurs in spleen cords
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What is haptoglobin?
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alpha globulin that binds free hemoglobin to prevent its excretion
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Where does most extravascular hemolysis occur?
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spleen cords/trabeculae
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In patients with hemolytic anemia, what happens to serum haptoglobin levels? Why?
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decrease; excess free serum hemoglobin quickly binds serum haptoglobin and is degraded by phagocytes
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In hemolytic anemia, build-up of what compound causes jaundice?
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un-conjugated bilirubin
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In a patient with hemolytic anemia, we may see a high number of what type of cells in a peripheral blood smear?
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reticulocytes
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Why may patients with hemolytic anemias be at high risk for gallstones?
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excess RBC degradation = high Hb in blood= high un-conjugated/insoluble bilirubin = collect in the bile ducts
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What is hereditary spherocytosis caused by?
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intrinsic defects in RBC membrane proteins (actin, spectrin, ankyrin etc.), causing the RBC to be less deformable = more lysis in spleen
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Why are RBCs with membrane protein defects spheres rather than biconcave discs?
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the proteins are working to keep the RBC as a biconcave disc, but are able to allow it deform in the spleen cords/trabeculae. without the proteins, the cell assumes the smallest diameter (sphere) and is less malleable (causing hemolysis)
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Why might patients with hereditary spherocytosis have splenomegaly?
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accumulation of degraded RBCs in the spleen trabeculae; and increased # of phagocytes migrating to degrade them
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In a patient with hereditary spherocytosis, what do we expect their MCHC to be? (higher or lower) Why?
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higher; the spherocytic RBC loses water (concentrating the hemoglobin) due to loss of K+ (water follows it out)
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Why does a defect in Glucose 6 Phospate dehydrogenase lead to anemia?
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G6PD is needed to prevent ROS (reactive O2 species) formation; without G6PD, RBCs are more susceptible to oxidative damage
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What does the enzyme glutathione peroxidase do?
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converts bad H2O2 into water
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Why do patients with G6PD defects experience crisis during infections?
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G6PD = more formation of Reactive O2 species. infections = higher leukocytes = higher lysosomal/peroxisomal activity = higher ROS already. compound effect of a lot of ROS will cause a lot of RBC damage
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In acute intravascular hemolytic anemia, why do we not see splenomegaly of gallstones?
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those are characteristics of chronic hemolysis (build-up of RBCs in spleen and un-conjugated bilirubin in the bile duct)
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What is HbA?
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Adult hemoglobin made of 2 alpha and 2 beta chains
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What is HbF?
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fetal hemoglobin; 2 alpha and 2 gamma chains (no beta chains)
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Sickle cells anemia is caused by a mutation of what hemoglobin chain?
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B
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What is HbS?
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sickle cell hemoglobin; 2 alpha chains and mutated beta chains (glutamate to valine)
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"Sickling" of mutated RBCs in sickle cell anemia is stimulated by what event?
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hypoxia, deoxygenation
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How do sickled RBCs lead to anemia?
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RBCs get caught in the spleen and are degraded
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Heterozygotes for the sickle cell trait have approximately what % HbS?
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40% of their hemoglobin is the HbS form (60% HbA)
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Why do infants with sickle cell disease not present with any problems until 5-6 months?
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until 5-6 months, HbF is the primary source of hemoglobin (has no beta chains so is unaffected by B chain mutation). then the infant will start making HbA (2 alpha, 2 beta chains), now there the beta mutations are visible
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Why are high levels (or persistence) of HbF helpful in patients with sickle cell anemia?
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sickle cell anemia is caused by a beta chain defect; HbF has no beta chains. it has a stronger affinity for oxygen so it is harder to get oxygen into their tissues, but better than having sickle cell risks
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What is HbC?
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a variant of sickle cell RBC hemoglobin; 2 alpha, 2 defective beta chains. glutamate to lysine substitution is less bad than the HbS mutation
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In a patient with HbAS RBCs, what % of their cells are in the HbS (sickle cell) form?
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40%; this patient is a carrier for sickle cell anemia
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What is HbSC disease?
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Patients with 1 copy HbS, 1 copy HbC; 50% HbS. has sickle cell symptoms
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High [HbS] can allow us to make what prediction about MCHC?
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MCHC increases. HbS cells have dehydration occur, making them more viscous. MCHC increases as water leaves
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Why would a decrease in pH lead to sickle cell crisis?
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low pH = Bohr shift to the right= oxygen leaves hemoglobin easier = more deoxy hemoglobin = sickling
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Why do vaso-occlusive sickle cell crises occur in microvascular beds?
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microvascular beds have very slow transit times of RBCs. the RBCs can slow down and aggregate much easier
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What is auto-splenectomy with relation to sickle cell anemia?
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accumulation of damaged RBCs in the spleen = splenic infarction/fibrosis/shrinkage
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What is B-thalassemia?
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defective production of B chains of hemoglobin; so excess alpha also
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Why does B-thalassemia (defective B chain synthesis) lead to anemia?
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low B chains = more alpha chains= alpha chains aggregate into insoluble groups with membranes damage = apoptosis
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What is B+ thalassemia?
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some beta chains are being made, but not enough
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What is B0 thalassemia?
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no beta chains are being made
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Most common cause of B+ thalassemia?
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splicing mutations
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Most common cause of B0 thalassemia?
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chain terminator mutations
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What is hepcidin?
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inhibitor of iron absorption
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What is B thalassemia major?
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patient with 2 affects B alleles (either B+/B+, B+/B0, or B0/B0)
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What is B thalassemia minor?
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patient with only 1 affected beta allele (B+/B, or B0/B)
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Why are patients with B thalassemia at high risk for iron overload (hemochromatosis)?
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B-thalassemia = poor membranes/A chain aggregation =apoptotic RBCs= ineffective erythropoiesis = low hepcidin = high iron absorption; patients are also likely getting transfusions that gives even more iron overload
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What is A-thalassemia?
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defective hemoglobin alpha chain synthesis= excess B chains
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What is HbH?
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a beta chain tetramer instead of normal HbA; seen in a-thalassemia where we can't make a chains; fairly stable, but has a really high affinity for oxygen (bad to get oxygen to tissue)
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Why is A-thalassemia less severe than B-thalassemia?
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a-thalassemia leads to an excess of beta chains which aggregate to form HbH. HbH can still bind some oxygen and function. In B-thalassemia, excess a chains aggregate and lead to RBC apoptosis, which is totally useless
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Would elevated levels of HbF help a patient with A-thalassemia?
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not really; HbF is useful in treating B-thalassemia because there is a problem with B chain synthesis, and HbF doesn't require B chain synthesis. patients with A-thalassemia have bad alpha chain synthesis, which would lead to bad HbF synthesis also (HbF has alpha chains, but no beta)
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What are hemoglobin Barts?
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excess gamma chains form a gamma4 tetramer instead of HbF in newborns with A-thalassemia
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Which is more likely to cause symptoms in a newborn? (A-thalassemia or B-thalassemia)
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A-thalassemia; B-thalassemia is a problem with beta chain synthesis. newborn using HbF don't need beta chain synthesis since HbF has no beta chains
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What is Hydrops Fetalis?
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formation of gamma tetramers (hemoglobin Barts) in newborns with A-thalassemia; fetal distress during pregnancy
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Why does Hydrops fetalis present in the 3rd trimester of pregnancy and not earlier?
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hydrops fetalis is caused by a defect in alpha chain sysnthesis; before the 3rd trimester of pregnancy fetal hemoglobin uses ζ instead of alpha
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What is paroxysmal nocturnal hemoglobinuria (PNH)?
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defects in PIGA (enzyme for cell surface protein synthesis) = less surface proteins to protect from degradation = more degradation by complement system= hemolysis
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What are immunohemolytic anemias caused by?
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antibodies bind to RBCs = destruction
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How does "Warm antibody" immunohemolytic anemia lead to hemolysis?
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IgG on RBCs bidn to Fc receptor on phagocytes = partial degradation = loss of membrane = change in RBC shape = spherocytes= rupture/trap in spleen
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What is "Cold Agglutinin" immunohemolytic anemia?
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IgM binds RBCs in low temperatures in extremities, and when it rewarms, IgM leaves before partial phagocytosis, but leaves some C3b (opsonin) to signal phagocytosis of RBCs
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What is "Cold hemolysin" immunohemolytic anemia?
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IgGs bind RBCs in cooler extremities, then when they warm in the rest of the body complement mediated lysis ocurs
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Megaloblastic anemias are generally caused by defects in ...
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DNA synthesis (B12/folate deficits)
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What is pernicious anemia?
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B12 deficit due to lack of intrinsic factor from parietal cells of stomach
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Why does B12 deficiency lead to defective DNA synthesis?
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B12 deficit = low FH4 = low dTMP = low DNA synthesis
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In patients with decreased B12, what do we expect to see regarding homocysteine levels? higher or lower?
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higher; without B12 homocysteine accumulates and can't be turned into methionine
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What is methotrexate?
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a folic acid antagonist; inhibits DNA synthesis; used in cancer therapy
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Iron is transported in the body by binding to what protein?
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transferrin (apotransferrin)
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How does hepcidin inhibit iron absorption into blood?
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hepcidin causes endocytosis/degradation of ferriportin = less iron can travel through the cell into the blood
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When the body has low levels of iron, what happens to hepcidin synthesis?
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hepcidin synthesis should decrease since we no longer want to prevent iron absorption. we want iron absorption now = less hepcidin
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Microcytic, hypochromic RBCs are created by what type of anemia?
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iron deficiency anemia
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To diagnose patients with iron deficiency, what would we see in their total iron binding capacity and ferritin levels?
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ferritin should be low (less iron=less storage). total binding capacity should be high (no iron = more capacity/spots available for iron to bind)
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How might a chronic disease state lead to anemia?
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certain cytokines (IL-6) can increase hepcidin levels = inhibit iron= bad hemoglobin
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What is a hypothesis as to why chronic infection would want to cause the body to decrease iron levels (increase hepcidin)?
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certain bacteria might use iron to survive, so we want to limit that ability
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An anemic patient has high serum ferritin levels and a reduced total iron binding capacity. Is his anemia caused by an iron deficit?
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no; iron defect = low ferritin since there isn't enough to be stored and high binding capacity. his patient has enough iron. the anemia is maybe B12 deficit or hemolytic
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What is aplastic anemia?
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bone marrow is not able to produce sufficient RBCs; perhaps due to damage, infection, radiation etc.
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Why will aplastic anemia always lead to reticulocytopenia?
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bone marrow defects= less formation of reticulocytes
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What is Myelophthisic anemia?
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cancer or other space occupying lesions replace bone marrow space = less RBC production
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Why might chronic renal failure lead to anemia?
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kidneys produce erythropoietin. bad kidney = less RBCs
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