anemia – Chemistry – Flashcards
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| what is the erythron? |
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| the entire circulating red cell mass, anemia is when this mass is decreased |
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| what are the primary causes of anemia? |
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| primary bone marrow disorders, susbstrate deficiency (no iron, protein)accelerated loss or destruction (bleeding or destroying), decreased erythropoietin (protein synthesized by distal peri-tubular cells in kindy, encoded on chr 7) |
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| what are the general steps of erythropoiesis? |
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| kidney senses hypoxia on RBCs, stimulates production of erythropoietin, bone marrow is stimulated to produce more RBC, increased RBCs eliminate hypoxia, erythropoietin levels return to normal. |
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| can erythropoietin be synthesized and administered to pts? |
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| yes, but if a kidney is damaged - it has to be replaced |
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| what are normal Hgb levels for a male? female? |
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| males: 14-26, females: 12-15 (male androgen are the reason their count is higher. menstruation doesn't really factor in.) |
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| what does a CBC (complete blood count) assess? |
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| RBC, Hgb, Hct, MCV, MCH, MCHC, RDW, WBC, platelet count, PDW, and PCV |
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| what should the RBC be in a CBC? |
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| 4-5 million |
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| what is the ratio of RBC to Hgb to Hct (hematocrit - % RBC in bloodstream)? |
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| 1:3:9 |
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| what is MCV and what should it be in a CBC? |
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| the mean corpuscular volume (how big cells are), should be generally 80-100. low: microcytic, high: macrocytic |
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| what is MCH? |
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| mean corpuscular hemoglobin - amount of Hgb per cell |
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| what is MCHC? |
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| the mean corpuscular hemoglobin conc - Hgb per hematocrit. low: hypochromic, high: hyperchromic. this is useful in determining spherocytosis (MCHC is high) |
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| what is RDW? what should it be in a CBD? |
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| red cell distribution width; variation in cell size - the greater the number, the greater the variation. 12-14 is normal |
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| what should the WBC be in a CBC? is there any racial variation? |
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| 5-10,000. african-americans tend to have a lower values here than caucasians |
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| what should the platelet count be in a CBC? |
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| between 150,000 and 450,000. this is an acute phase reactant that will go up and down |
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| what are PDW and PCV? |
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| PDW - platelet distrobution width (same as RBC, but for platelets), PCV - same same as MCV, but for platelets |
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| how are RBCs affected by pregnancy? |
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| more iron is needed everyday. RBC mass will increase to respond to higher O2 need. RBC volume will then increase and plasma volume increases even more than RBC mass. they appear to have a lower Hgb b/c of this higher volume |
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| what is a reticulocyte? |
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| the last step before a cell becomes a RBC. |
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| how long to RBCs last? what is the turnover rate? |
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| 120 days, the turnover rate is .8%/day so everyday ~ 1% of RBCs will die and be replaced. |
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| what does a reticulocyte count tell you? |
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| how many RBCs are being made; low:hypo-/high: hyperproliferative |
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| how is a reticulocyte count performed? |
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| a blood smear is stained for reticulum, and a ratio is taken out of 1000. the value is expressed as a % - but is not indicative of other cell levels, so it only useful comparatively rather than as an individual value |
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| what is an absolute retic count? |
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| the retic count is multiplied by the RBC value, this will give you the # of retics |
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| what is an absolute corrected retic count? |
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| retic counts take 4 days to develop (3 days in the bone marrow, 1 day in the periphery). for each 10 pt drop in hematocrit, retics spend an extra 1/2 day in the periphery (bone marrow kicks out retics faster in anemia). so to correct for this 1/2 day, the absolute retic number is divided by the # of days in the periphery. so assuming a hct of 45 is normal, if you have 35 you divide by 1.5, if you have 25, you divide by 2, if you have 15, you divide by 2.5 etc. this will show anemics having lower retic values that previously, which is the actual representation of what is going on in the body b/c the retics are being pushed out faster than normal |
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| what should the absolute retic count be? would this go up if a pt is anemic? |
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| between 25-75,000. this will rise in anemia (body is trying to compensate) |
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| what is the retic index? |
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| the same thing as an absoulte retic count, but just expressed as a ratio where 1 is normal (higher is good, lower is bad). the hematocrit is divided by 45 and multiplied by the retic % from the lab ( %x(hct/45)) |
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| what are reasons for a low reticulocyte count? |
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| the bone marrow is not responsive due to: aplasia (no cells in bone marrow - seen w/leukemia), bone marrow suppression (drugs/alcohol, viruses can do this), dysplasia (abnormal cells, seen in myelodysplastic syndromes - cells may live for shorter amounts of time) |
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| what should be considered if a pt's retic count is normal? |
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| their Hgb. if this is normal as well, everything's good - but if it is low, the person is likely severely anemic |
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| what does a high retic count mean? |
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| the body has recognized anemia and is trying to compensate (erythropoietin is not usually necessary if pt is young and healthy). if a person is still anemic with a high retic count, you have to determin if they are bleeding or destroying RBCs |
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| what do retics look like? |
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| they are larger than RBCs, and tend to have a grey hue, and have to be specifically stained for otherwise the best assessment that can be made in terms of which cells are retics is that some cells have polychromasia (many colors, when this is noted a retic count is ordered) |
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| how is anemia classified? |
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| usually first according to size. microcytic (less than 6 microns or MCV is less than 80), macrocytic (greater than 9 microns or MCV greater than 100). normocytic is everything inbetween |
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| what are some differentials for microcytic anemia? |
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| iron deficiency, thalassemia, sideroblastic anemia, lead/heavy metal, things that affect Hgb synthesis, anemia chronic disease (chronic inflammatory state) |
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| what do RBCs affected by microcytic anemia appear in terms of size? color? |
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| RBC should be the same size as the nucleus of a small lymphocyte. the white central pallor of a RBC should be 1/3 the diameter, if it is any greater - hypochromic |
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| what is seen in terms of platelets in anemia? |
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| an increase |
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| what are common clinical presentations for anemia? |
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| tired, no energy, heart racing, shortness of breath. rarer: coiling of nails (koilonychia), like to eat ice/red clay, glossitis (smooth painful tongue), angular stomatitis (sores on corner of mouth), postcricoid esophageal web/stricture, pallor, heart palpiptations, tinnitus (more pounding), headaches, irritability, weakness/dizziness/easily fatigued |
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| when do anemics start showing symptoms? |
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| when Hgb is low |
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| why is iron deficiency uncommon w/the western diet? |
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| avg iron requirement is ~1 mg/day and the avg western iron intake is 16 mg/day. this is not usually a problem unless the pt is bleeding or a strict vegan |
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| what are normal lab values for iron? |
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| marrow iron stores: 2-3, transferrin: 330, ferritin: 100, iron 100-500 |
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| how do iron lab values change when you first start to loose blood? what about if blood loss continues? if it continues even more? |
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| serum iron level will temporarily dip, iron stores will drop, transferrin will stay the same, plasma ferritin stores will go down, and plasma iron will be a little low. marrow iron stores will be used up, transferrin increases, plasma ferritin drops, and plasma iron is lower. if blood loss keeps continuing: no iron stores, high transferrin, low ferritin, low plasma iron - this is the iron deficient state |
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| what is the $/iron analogy? |
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| ferritin: bank account, transferrin (iron binding capacity): credit card, pocket money: plasma/serum iron |
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| what is the first thing you fix in iron deficient anemia? |
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| the last thing that went wrong. this is the progression: anemia fixed, serum iron fixed, then transferrin, ferritin. (when you replace someone’s iron you shouldn’t stop when anemia goes away – hemoglobin will be normalized, but you’ll still have no iron stores – if you stop giving iron then they will go right back to where they were) |
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| how is iron administered? what is its half life? what else needs to be done beyond administration of iron in deficiency? |
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| 3x/day (unless the pt cannot tolerate it). iron has an infinite t 1/2. whatever is causing the deficiency needs to be determined. |
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| what are lab results consistent with iron deficiency? |
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| MCV less than 80 (microcytic), high RDW, hypochromic, low ferritin/transferrin/serum iron levels, genetic/electrophoretic evidence of thalassemia (defect in hgb chain) |
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| what is the mentzer index? |
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| MCV/RBC. if less then 30 = thalassemic, if greater than 14 = iron deficiency (not dx, but suspicious) |
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| what are other causes than bleeding (main cause in US) for iron deficiency? |
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| hemoptysis (coughing up blood), epistaxis (nosebleeds), blood donation, malabsorption (GI sx, intestinal malabsorption), GI bleeds, and pregnancy |
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| what needs to be ruled out with anemic older pts? |
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| colon CA/GI bleeds |
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| what kinds of GI bleeds can cause anemia? |
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| GI bleeding (tumors/oesophageal varices, hemorrhoids, AVM, gastritis, duoenitis, peptic ulcers), GU bleeding (bladder tumor), GYN bleeding (ask about tampon #/period frequency), helminthic infections (hookworm, schistosoma, trichuris) |
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| how is iron deficiency treated? how long do you treat? |
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| stop the cause of bleeding, supplement with iron (oral (best), IM (Z tract injection and lills muscle), IV via iron dextran (possible allergy), sucrose, or gluconate). **treatment is until the iron stores are better. |
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| what is thalassemia? |
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| beta chain thalassemia is a defect w/2 genes on chr 11 and is common w/mediterranean, african and middle easterners. alpha thalassemia is a problem w/4 genes on chr 16 and is seen in SE asian and middle eastern pts. (hgb is 4 proteins wrapped around an iron molecule, 2 alpha/2 beta) |
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| what are the types of beta thalassemia? |
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| minor/heterozygotic: beta production is about 1/2 normal. major/homozygotic: beta0 (naught) – makes no beta chains or more commonly, beta+ – makes some beta chains – 5 to 40% |
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| what are the types of hemoglobin? |
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| A: alpha2beta2(normal), A2: alpha2delta2, F: alpha2gamma2, H:beta4, and barts: gamma4 |
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| how do pts with beta thalassemia generally present? |
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| usually asymptomatic, but they can have a massive proliferation of bone marrow causing skeletal deformities w/major thalassemia. they will need bone marrow transplants due to iron overload (blood transfusions caused iron overload) |
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| what is seen on an x-ray for pts w/beta thalasemia? |
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| "hair on end appearance" due to hyperproliferation of marrow |
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| what does the mentzer index *usually show in cases of beta thalassemia? RDW? hgb/RBC? |
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| a mentzer index (MCV/rbc) count of less than 13 favors thalassemia. RDW is normal - cells tend to be the same size. if in the RBC/Hgb/Hct ratio of 1:3:9 ratio you see <3, thalassemia is suspicious |
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| how does beta thalassemia appear on a lab smear? |
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| codocytes (target cells) are visible |
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| what will be low in beta thalassemia? what will this cause? |
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| hemoglobin A, which will lead to hypochromic cells and a massive decrease in mature RBC production |
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| what will there be more of in beta thalassemia? what can happen w/these? |
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| alpha chains (due to lack of beta chains to pair up w/), which can cause inclusion bodies in red cell precursors and eventually kill them, so the spleen has to get rid of these leading to hypersplenomegaly -> may cause jaundice/gall stones |
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| what can beta thalasemia possibly lead to? |
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| profound anemia, heart failure, infections, tissue becoming hypoxic, increased erythropoietin, massive expansion of bone marrow (hair on end appearance), GI problems, and deformities |
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| why is alpha thalassemia more complicated than beta? |
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| b/c it involves 4 genes rather than 2. |
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| what happens if a pt with alpha thalassemia has 1 gene deletion? 2? |
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| 1 gene deletion: is called alpha thal 2 trait, and people are usually fine (xa/aa). 2 gene deletion: is called alpha thal 1 trait cis if same chr (mediterranean/asian) (xx/aa) OR alpha thal 1 trait trans if different chr (african) (xa/xa) |
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| what happens if a pt with alpha thalassemia has 3 gene deletiona? 4? |
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| 3 alpha hgb chain gene deletions is called hgb H disease, and there is a increase of left over B chains. all 4 gene deletion = hydrops fetalis, infants will be born dead |
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| what are possible outcomes for a child born to to alpha thal 1 trait cis parents? |
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| 50% chance child will be alpha thal 1 trait cis also, 25% chance they will be normal and 25% chance of hydrops fetalis |
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| what will a child be from 2 alpha thal 1 trait trans parents? |
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| 100% probability they will be alpha thal 1 trait trans as well |
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| what is therapy for thalassemia pts? |
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| genetic counseling (esp for alpha thal 1 trait cis), transfusions/bone marrow transplants for beta thalassemia major, and for alpha thalassemia types with 1 or 2 deletions no tx, for pts with 3 deletions - possible splenectomy/transfusion |
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| why must iron deficiency be differentiated from thalassemia? |
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| the body doesn't have a mechanism to get rid of iron. if a pt with thalassemia is treated with iron, they will not improve and iron overload can eventually destroy the liver/pancreas. (people should respond to iron within wk/mos) |
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| do american adults typically need iron supplements? |
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| no |
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| what kinds of anemia might present as normocytic? |
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| iron deficiency (after a massive bleed and not enough time has passed to make microcytic cells), anemia chronic disease (chronic inflammatory state), anemia of renal failure (kidneys don't work and erythropoietin goes down), marrow failure (marrow is slow/doesn't make enough) |
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| what is seen in lab results for iron deficiency? |
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| RDW increases first due to an intial brisk reticulocytosis, early hemorrhage (which is why microcytic indexs aren't necessarily seen) and later developing anemia |
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| what is seen clinically for iron deficiency? |
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| malaise, pallor, palpitations, ringing in the ears, headache, irritability, weakness, dizziness, etc |
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| what is the pathophysiology of anemia of chronic disease (ACD)? |
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| cytokines and free radicals damage erythroid precursors causing a disorder of iron hemostasis (not released from ferritin (synthesis of which is also increased) and not incorporated into RBC as readily) |
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| what do cytokines IFN gamma, LPS, IL-10, and TNF-alpha do in ACD? |
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| IFN gamma, LPS, and TNF-alpha all upregulate DMT1 (divalent metal transporter 1) which is responsible for transmembrane import of ferrous iron - this increases the uptake of iron into macrophages. these cytokines also down-regulate ferroportin which blocks release of iron from cells through the transmembranous iron transporter. IL-10 stimulates transferrin mediated acquisition of iron by macrophages |
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| what is hepcidin? how is it involved with ACD? what will high hepcidin in mice cause? |
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| hepcidin is an iron-regulating acute phase reactant that is induced by LPS/IL-6 and is inhibited by TNF-alpha. this diverts iron traffic through the duodenoum and inhibits release of iron from macrophages. high hepcidin in mice will cause iron deficiency anemia. |
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| how does IL-6 play a part in ACD? |
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| IL-6 induces hypoferremia |
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| what is the difference between iron deficient anemia and ACD? |
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| in ACD: IL-1, interferon alpha, interferon beta, interferon gamma, TNF alpha all down regulate erythropoietin receptors - if you have decreased receptors have decreased responsiveness to erythropoietin, therefore decreased red cell production. in ACD: transferrin receptors will be low, ferritin will be high, and iron binding capacity will be low |
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| what should be looked for *first clinically in terms of ACD? |
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| look for signs of underlying chronic inflammatory disease: RA, acute/chronic infections, CA, SLE, vasculitis, sarcoid, IBD |
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| what is seen on lab results for pt wih ACD? |
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| usually mild anemia, hgb ~9.5, a little fatigue, low retic count, low iron, low iron sat, low to normal IBC, high ferritin (different than iron deficiency anemia), normal or low transferrin receptors |
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| what is the treatment for pts with ACD if the underlying chronic disease cannot be treated? |
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| iron and erythropoietin supplementation |
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| what are the stages of chronic kidney disease? |
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| 90ml/min is stage one, divide in half down to stage five |
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| what happens in terms of anemia w/renal failure? |
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| impaired erythropoietin and subsequent decreased rbc production as well as uremic toxins that impair proliferation of erythroid precursors (spermine, PTH, and ribonuclease). these problems are treated with erythropoietin and dialysis respectively. |
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| how do pts with anemia due to renal failure present? |
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| usually fine - symptoms of renal failure will present before the symptoms of anemia |
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| what is seen in terms of lab results with renal failure related anemia? |
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| serum creatinine (mostly cleared by filtration), GFP (glomerular filtration rate assessed w/cockoff gault formula, graded 1-5), serum erythropoietin, (semi log curve - more anemic = higher erythrpoietin) |
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| how is anemia due to renal failure treated? |
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| erythropoietin/dialysis, renal transplant or repair |
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| what happens with bone marrow failure? what is this associated with? |
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| the bone marrow can no longer make retics and may show pure red aplasia which is associated with malignant thymomas. it may also show complete aplasia, where nothing in the bone marrow will work and dacrocytes (misshapen tennis racket cells) will also be visible. |
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| what is falconi's anemia (aplastic)? how is it tested for? |
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| an autosomal recessive aplastic disease due to defects in the DNA excision repair pathway. these pts are unable to remove ROSes. it can be dxed with a bone marrow bx. |
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| what are clinical features of pts with fanconi's anemia? |
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| skin pigment changes, short stature, upper limb abnormaility, hypogonadism (male), skeletal changes, eye abnormalities, kidney malfunction, ear anomaly with deafness, and GI/heart abnormalities |
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| what are lab results consistent with fanconi's anemia? |
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| bone marrow failure; first manifested by thrombocytopenia and last by a decrease in hematopoietic lineages. granulocytopenia is also seen along with chromosomal fragility, (chromatid breaks, rearrangements gaps etc) |
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| what is the treatment for fanconi's anemia? |
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| bone marrow transplant |
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| what is the treatment for marrow failure if it is an immune related failure? |
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| immune therapy; ATG, cyclosporine A, and a bone marrow transplant |
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| if a pt has macrocytic anemia, what should be on the differential? |
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| *alcohol*, *B12 deficiency*, *folic acid deficiency*, drugs (that interfere w/folic acid), liver disease (misincorporation of cholesterol into RBCs), hypothyroidism (sluggish), reticulcytosis (too many retics - machine thinks they are large RBCs), myelodysplasia (damaged bone marrow) |
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| what tests should be done to dx macrocytic anemia? |
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| get B12, folic acid levels (both serum (gives immediate level) and RBC (shows more long term level)), peripheral smear to check for large, hyper segmented neutrophils (due to abnormal DNA b/c of lack of folic acid for DNA repair), thyroid function tests to make sure not hypothyroid, liver function test to make sure liver isn't shutting down, and bone marrow bx |
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| where does folic acid come from? |
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| green leafy vegetables (folia - latin for leaves) |
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| how do pts with a B12/folate deficiency present? |
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| pallor w/yellow tint (sallow), premature greying, pigmentation of skin increases/nail beds, mask like faces (folate), beefy red tongue, and neurologic signs (posterior while columns - proprioception/vibrioception) |
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| what is seen clinically with B12/folate deficiency? |
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| hypersegmented PMNs |
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| what is pernicious anemia? |
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| anti intrinsic factor/antiparietal cell antibodies that block the absorption of B12 |
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| how is pernicious anemia tested for? |
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| anti-intrinsic factor/anti-parietal cell antibodies are tested for |
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| how are B12 and folate deficiencies treated? |
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| B12/folate are administered orally or via IV/IM/nasal (shots are 1x/mo) |
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| what are the 2 possible reasons hemolytic anemia? |
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| immune or intrinsic/extrinsic factors |
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| how does the immune system cause hemolytic anemia? how is this tested for? |
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| the body can make antibodies that attack RBCs and coombs test is for this. the coombs test checks RBCs for antibody, and the indirect coombs test checks the serum for antibody. warm antibodies are IgG/cold are IgM & C3. microspherocytes are also seen b/c the spleen chops off the antibody, and with it some of the membrane = leaving smaller sphere RBCs that have lost their biconcave shape. |
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| can hemolytic anemia be intra or extravascular? |
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| both |
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| what could be responsible for extrinsic hemolytic anemia? |
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| waring blender syndrome which is an abnormal heart valve, a kesselbach merrit AV shunt, DIC (fibrin strands cutting RBCs into schistocytes - microangoipathic), and membrane problems (spherocytosis/elliptocytosis) can all lead to hemolytic anemia |
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| what are intrinsic problems that can cause hemolytic anemia? |
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| hemoglobin problems (sickle cell and hgb C), enzyme problems (G6PD deficiency - this makes NADP into NADPH, without which you get oxidative stress) |
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| what is G6PD seen in? what can cause the exacerbating oxidative stree? |
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| african americans, oxidative stress can come from: infection, sulfa drugs, and fava beans |
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| how does hemolytic anemia present clinically? |
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| jaundice (scleral icterus/intravascular), splenomegaly, and pallor, fatigue etc |
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| what lab results are consistent with hemolytic anemia? |
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| bilirubin (what hemoglobin is broken down into, indirect is usually higher than direct), haptoglobin levels drop (b/c they bind globin portion of hgb), LDH levels will be high intracellularly, and hemodesiderin (metabolized hgb) will be found in urine |
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| what is tx for hemolytic anemia? |
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| treat underlying cause (could be abnormal heart valve, AV malfunction, DIC), mediate immune system with steroids, avoid drugs that cause enzyme problems (like w/G6PD), -> treat rapidly |
