Term
|
Definition
| Normocytic w/high RDW (normocytic with normal RDW in heterozygotes) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| hypercellular, may develop BM fibrosis (unless the pt is in an aplastic crises, which decreases BM production) |
|
|
Term
| Sickle cell reticulocytes |
|
Definition
|
|
Term
| Sickle cell peripheral blood smear |
|
Definition
| Sickle cells and some target cells |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Infection by parvovirus causes an arrest of erythropoiesis in the bone marrow. Pts with HS and sickle cell continue to hemolyze but because their ability to produce new rBCs is temporarily stopped, they become severely anemic and reticulocytopenic. Bone marrow that is usually hypercellular decreases in cell count in this crisis |
|
|
Term
| HS peripheral blood smear |
|
Definition
|
|
Term
|
Definition
| Hypercellular with compensatory erythroid hyperplasia, unless in an aplastic crisis |
|
|
Term
|
Definition
| - Young child of Northern European descent and a parent with the condition that is presenting with fatigue and splenomegaly. May have bilirubin/pigment gallstones in childhood |
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|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Bite cells and blister cells. Caused by macrophages in spleen grabbing out precipitated hb (Heinz bodies) that collapsed when oxidative damage destroyed the h-bonds. Bite cells are quickly removed by spleen. There are also spherocytes and schistocytes frequently |
|
|
Term
|
Definition
| Erythroid hyperplasia during hemolytic episode |
|
|
Term
| G6PD other diagnostic clues |
|
Definition
- Episodic anemia after oxidative stress
- Mediteranean, Middle Eastern, African descent
- Family history (X linked) |
|
|
Term
| Autoimmune hemolytic anemia MCV |
|
Definition
|
|
Term
| Autoimmune hemolytic anemia |
|
Definition
| Hemolytic anemia that is due to extrinsic red cell defects (not inherent abnormalities of red cells themselves). But like intrinsic red cell defect causing anemias, in AIHA, the blood cells are cleared by the spleen (extravascular). Autoantibodies against red cells, causing rapid clearnace of RBCs by spleen (extravascular clearance). Can be detected w/Coombs test |
|
|
Term
| Autoimmune hemolytic anemia peripheral smear |
|
Definition
| A good number of spherocytes, and a ton of reticulocytes (as opposed to HS which has a ton of spherocytes and a good number of reticulocytes) |
|
|
Term
| Microangiographic hemolysis MCV and RDW |
|
Definition
|
|
Term
| Ineffective erythropoiesis |
|
Definition
| Hypercellular marrow with erythroid hyperplasia but a low reticulocyte count. Seen in iron deficiency anemia and megaloblastic anemia |
|
|
Term
| Microangiographic hemolysis peripheral blood smear |
|
Definition
|
|
Term
| Iron deficiency anemia MCV and RDW |
|
Definition
|
|
Term
|
Definition
| Protein produced by the liver in presence of high levels of IL-6. Blocks iron release from macrophage stores and iron intake from GI mucosal cells. Does this by inducing destruction and internalization of ferroportin, the channel by which iron is passed into and out of cells. Although iron stores in ACD patients are adequate or even abundant, the transfer of iron into erythroid precursors doesn't occur; thereofre, the cells themselves are iron deficient and hb cant be synthosized. |
|
|
Term
| Iron deficiency anemia reticulocytes |
|
Definition
|
|
Term
| Iron deficiency anemia peripheral smear |
|
Definition
| Hypochromic and microcytic |
|
|
Term
| Iron deficiency anemia ferritin |
|
Definition
|
|
Term
| Iron deficiency anemia TIBC saturation |
|
Definition
|
|
Term
| Iron deficiency anemia bone marrow |
|
Definition
| Mild to moderate erythroid hyperplasia/ineffective erythropoiesis |
|
|
Term
| Megaloblastic anemia MCV and RDW |
|
Definition
| Macrocytic w/high RDW. Macrocytic bc Hb is still high |
|
|
Term
| High cytokines and erythropoietin |
|
Definition
| Decrease epo. That is why epo levels in ACD are low relative to the degree of anemia |
|
|
Term
| Megaloblastic anemia reticulocytes |
|
Definition
|
|
Term
| Megaloblastic anemia peripheral smear |
|
Definition
| Macroovalocytes, leukopenia and thrombocytopenia in advanced cases, hypersegmented neutrophils |
|
|
Term
| Megaloblastic anemia bone marrow |
|
Definition
| Hypercellular with erythroid hyperplasia/ineffective erythropoiesis and markedly abnormal looking erythroid and granulocytic precursors |
|
|
Term
| Anemia of chronic disease/inflammation MCV and RDW |
|
Definition
| Microcytic to normocytic (low iron available to the cell so low Hb and low cytoplasmic volume) and normal RDW |
|
|
Term
| Anemia of chronic disease cause |
|
Definition
| Secondary to another systemic disease- inflammatory, autoimmune, or cancer. In these situations, there are high levels of inflammatory cytokines that 1. shorten RBC survival due to inflammatory plasma 2. Decrease epo release 3. IL-6 stimulates hepcidin release from liver, which blocks iron release from macrophage stores and blocks dietary iron transfer from GI mucosal cells into the plasma by degrading ferroportin |
|
|
Term
| Anemia of chronic disease/inflammation reticulocytes |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Erythroid hypoplasia. Abundant storage iron but no iron bearing erythroid precursors (sideroblasts) when stains for iron are done |
|
|
Term
| Anemia chronic renal failure MCV and RDW |
|
Definition
| normocytic with normal RDW |
|
|
Term
| Anemia chronic renal failure reticulocyte |
|
Definition
|
|
Term
| Anemia chronic renal failure peripheral smear |
|
Definition
|
|
Term
| Anemia chronic renal failure RDW |
|
Definition
|
|
Term
| Anemia chronic renal failure peripheral blood |
|
Definition
|
|
Term
| Anemia chronic renal failure bone marrow |
|
Definition
| Similar to ACD. Diminished cellularity, reduced erythropoiesis, abundant iron stores |
|
|
Term
|
Definition
| Normo to macrocytic anemia |
|
|
Term
|
Definition
|
|
Term
| Aplastic anemia reticulocytes |
|
Definition
|
|
Term
| Aplastic anemia peripheral blood |
|
Definition
| Pancytopenia, elevated HbF (stress erythropoiesis causing upregulation of all globin chains) |
|
|
Term
| Aplastic anemia bone marrow |
|
Definition
|
|
Term
| Aplastic anemia other clinical clues |
|
Definition
| Frequent infections and bleeding in addition to anemia as a result of pancytopenia |
|
|
Term
| Hematocrit and how to calculate |
|
Definition
| What percent of total blood volume is occupied by RBC. Hct=MCV (volume of an average RBC) X RBC count |
|
|
Term
| Is hemoglobin measured or calculated? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Major site of RBC clearance is the spleen (reticuloendothelial csystem/fixed macrophages in splenic cords) |
|
|
Term
| What 4 types of anemia are intrinsic hemolysis (inherited and extravascular/spleen mediated hemolysis) |
|
Definition
| 1. HS 2. G6PD deficiency 3. Hemoglobinopathy/SS 4. Thalassemias |
|
|
Term
| What two types of hemolytic anemia are extrinsic/intravascular/acquired hemolysis? |
|
Definition
| 1. Immune mediated hemolysis 2. Physical mediators/microangiopathic **Both have high RDWs, but immune mediated is macrocytic while microangiopathic is microcytic |
|
|
Term
| 3 Lab markers of increased RBC turnover (for hemolytic anemia) |
|
Definition
| 1. Increased lactate dehydrogenase (found in cytosol of RBCs) 2. Elevated bilirubin (from heme) 3. Decreased haptoglobin (what picks up free heme in the blood) |
|
|
Term
| HS cellular biology and genetics |
|
Definition
| AD mutations in ankyrin or band. Spectrin is the major structural protein in RBCs, and is held to the membrane by ankyrin and band. Mutations cause spectrin dimer release, the influx of intracellular sodium, and membrane instability w/loss of RBC membrane due to shearing stresses in the blood, and the assumption of a spherical shapte to maintain cell volume (anemia is normocytic with a high RDW). Cells are inflexible and are ultimately detained in and removed by the spleen prematurely |
|
|
Term
|
Definition
| Massive hemolysis (splenic RBC clearance) triggered by infection. In HS and HbSS when the pt still has a spleen (when the spleen hasn't completely autoinfarcted) |
|
|
Term
| G6PD deficiency variannts |
|
Definition
| A-:10-15% of enzyme activity M= 1%; may be a chronic condition in Mediterraneans. Women with is (heterozygotes) are resistant to falciform malaria |
|
|
Term
|
Definition
| H bonding is weakened in hb and the hb precipitates in the cell prompting removal by the spleen. This is why RBC survival is shortened in G6PD deficiency |
|
|
Term
|
Definition
|
|
Term
| Oxidative stresses causing hemolysis in G6PD deficiency |
|
Definition
| Anti-malarials (primaquine, chloroquine, pentaquine), anti-bacterials (sulfa drugs), fava beans, mothballs, many viral and bacterial infections, viral hepatitis, pneumonia |
|
|
Term
|
Definition
| Heinz body preparation from blood smear, measure G6PD levels when not in crisis |
|
|
Term
| Scleral icterus and discolored urine |
|
Definition
| Signs of hyperbilirubinemia/hemolytic anemia |
|
|
Term
|
Definition
| Think hemoglobinopathy (sickle cell), thalassemia, HS |
|
|
Term
|
Definition
| Structurally abnormal hemoglobin that functions poorly and causes pathologic changes to the red cells; caused by a mutation in the Coding region of a globin chain gene |
|
|
Term
|
Definition
| Decreased synthesis of structurally normal globin chains due to mutations or deletions in regulatory regions (for beta thal) or coding regions (for alpha thal) of globin chain genes. Transcribed mRNA is abnormal, has a short half life, and cannot be translated into protein |
|
|
Term
| Sickle cells is clinically recognized as... |
|
Definition
| Crises. 1. Vasoocclusive 2. Sequestration in those w/residual spleens 3. Aplastic crises |
|
|
Term
|
Definition
| Beta globin chain mutation alters hydrogen bonding and stability of globin chain interactions. In stress, HbS polymerizes, first reversibly but later irreversibly, which damages the RBC membrane. Damage to the membrane causes an influx of calcium and a loss of water, and the cell becomes more sticky and takes on a sickle shape. The sickle shaped cells occlude vessels and are prematurely removed by the spleen. Intracellular dehydration=increased amount of Hb=increased propensity for sickling. Other varieties of Hb in the cell decrease the propensity for sickling |
|
|
Term
|
Definition
| Supportive (transfusions, hydration), alkylating agents like hydroxyurea to increase HgF, folate (needed to make new Hb, so if you're hemolyzing a lot, help out by making sure there are enough materials for Hb production), penicillin prophylaxis (increased risk of infection w/o spleen), chelation of iron (remove excess iron) |
|
|
Term
|
Definition
| Detects bound red cell autoantibodies in autoimmune hemolytic anemia |
|
|
Term
| MIcroangiographic hemolysis |
|
Definition
| Hemolytic anemia where red cell survival is markedly shortened due to physical trauma w/in the vascular space. Intravascular clearance! Almost always secondary accompaniment to another, more clinically important disorder that is causing the microangiopathy, including DIC, systemic lupus erythematosus, arteritis, malignant hypertension, and prosthetic heart valves. Therapy is directed at the underlying condition causing hemolysis. Heat and infectious agents can also cause intravascular hemolysis. |
|
|
Term
| Three stages of iron deficiency |
|
Definition
| 1. Iron depletion (negative iron balance; iron stores decresing but not depleted, GI iron absorption increased, serum ferritin drops) 2. Iron deficient erythropoiesis, still not anemic 3. Iron deficiency anemia (normocytic becoming microcytic) |
|
|
Term
| What kind of a pt would have iron deficiency? |
|
Definition
| Growing, menstruating, post-gastrectomy, sprue, disease of proximal small bowel, after gastric surgery (impaired acidity that is necessary for absorption), chronic bleeding |
|
|
Term
| Iron deficient erythropoiesis |
|
Definition
| 2nd step in iron deficiency anemia. Fe is close to depleted and serum markers of homeostasis are abnormal, but there is no anemia (CBC is normal and they are asymptomatic) |
|
|
Term
| Serum iron studies in iron deficiency anemia |
|
Definition
| Low serum iron, low ferritin, high TIBC and low tranferrin saturation |
|
|
Term
|
Definition
| Large store relative to consumption and small daily loss. Absorbed by binding to IF secreted by parietal cells of the gastric mucosa. This complex is absorbed in the terminal ileum, and then enters the circulation bound to transcobalamin. Once in the cell, it serves as a cofactor for methyltransferase in a reaction in which tetrahydrofolate is generated. This rxn is critical for synthesis of thymidine. |
|
|
Term
|
Definition
| An enzyme that uses vit B12 as a cofactor in the production of tetrahydrofolate, which is necessary for thymidine synthesis. |
|
|
Term
|
Definition
| Disease of disordered immunity. Pts make autoantibodies against the gastric parietal cells that make intrinsic factor. W/o IF, there is no B12 absorption and you get megaloblastic anemia and neurologic symptoms (neuropathy, cerebellar signs, etc.) |
|
|
Term
| Four causes of B12 deficient megaloblastic anemia |
|
Definition
| 1. Pernicious anemia 2. Gastrectomy syndroms (removal of parietal cells that produce IF) 3. Intestinal disorders (B12 is absorbed in the ileum)- ileal resection, ileitis, intestinal tapeworms, malabsorption syndroms 4. Dietary deficiency in strict vegans and ppl w/chronically marginal diets |
|
|
Term
|
Definition
| Used up in rxns in which it participates, so deficiency can develop fairly quickly. Folate is absorbed in the proximal jejunum. It accepts a methyl group from B12 (cobalamin) and proceeds down a metabolic pathway through several intermediates to thymidine synthesis. |
|
|
Term
| 3 causes of folic acid deficiency |
|
Definition
| 1. Dietary deficiency (and prolonged cooking) 2. Impaired absorption (interfere w/folate absorption adn include malabsorption syndromes and diffuse intestinal disease) 3. Increased requirements |
|
|
Term
|
Definition
| 1. Methyl donor in thymidine synthesis 2. Role in myelin synthesis in CNS |
|
|
Term
|
Definition
| Final intermediary in thymidine synthesis |
|
|
Term
| Giving folate to B12 deficient patients? |
|
Definition
| Corrects the anemia, but neurological symptoms seen in B12 deficiency will not improve |
|
|
Term
| Tx for folic acid deficiency |
|
Definition
| Oral supplementation except in cases of GI disease |
|
|
Term
|
Definition
| parenternal supplementation (IM) |
|
|
Term
|
Definition
| Iron bearing ereythroid precursor. No sideroblasts in ACD, iron deficiency |
|
|
Term
| What accounts for anemia in anemia of chronic renal failure? 2 |
|
Definition
| 1. Decreased epo 2. Toxic plasma and bleeding (platelet malfunction) lead to decreased life of RBC |
|
|
Term
| 30% of aplastic anemia is caused by |
|
Definition
| Toxic exposure to drugs, chemicals (benzene), or infections (hepatitis). In 70%, there is no etiologic agent |
|
|
Term
| In the 70% of cases in aplastic anemia w/o an etiologic agent, bone marrow failure may be related to what two things? |
|
Definition
| 1. An acquired abnormality of the stem cell that leads to increased susceptibibility to injury (acquired mutation) 2. Immune suppression of stem cells by auto-reactive T lymphocytes |
|
|
Term
| Aplastic anemia typical pt |
|
Definition
| Presents at any age and affects the genders equally. Symptoms are typically fatigue, pallor, bleeding is most common, infection |
|
|
Term
|
Definition
| Transfusions. If an inciting agent is identified, removal may cure. In idiopathic forms, may try immunosuppressive drugs; if not, bone marrow transplantation is essential. |
|
|
Term
| Bone marrow in beta thalassemia and why |
|
Definition
| Aggregates of alpha globin chains are toxic to the cell, so the precursors die in the bone marrow->ineffective erythropoiesis |
|
|
Term
| What contributes to the anemia in beta thal? |
|
Definition
| Both precursor death in the marrow (production problem; alpha aggregates are toxic and precursors die), and a hemolytic problem bc abnormal cytoplasmic contents in those that escape to the blood stream are quickly cleared by the spleen |
|
|
Term
| Homozygous beta thal clinical presentation |
|
Definition
| Severe anemia that presents in infancy with failure to thrive, lethargy, irritability, jaundice, splenomegaly, and bony abnormalities. Transfusion therapy is initiated early. See end-organ damage from chronic hypoxia. iron overload from transfusions and increased iron absorption in the GI tract leads to heart failure and diabetes. Hepatosplenomegaly occurs due to extramedullary erythropoiesis. Life-shortening condition. |
|
|
Term
| Thalassemia major peripheral smear |
|
Definition
| Homozygous beta thal. Target cells, very hypochromic, some nucleated precursors escaped as bone marrow is whipped with epo |
|
|
Term
| Beta thal deletions in... |
|
Definition
|
|
Term
| Alpha thal deletions are in |
|
Definition
|
|
Term
| Ethnicities associated w/alpha thal |
|
Definition
| African, middle eastern, asian |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Two deletion alpha thal. Like heterozygous beta thal: mild microcytic anemia, few symptoms. May either be African deletion pattern, where each chromosome has one deletion, and two ppl with this deletion pattern have no chance of having a four deletion alpha thal child, or Asian deletion pattern, where one chromosome is missing both copies. Target cells on smear |
|
|
Term
| African vs asian deletion patterns in alpha thal |
|
Definition
| This is for thal trait, where the person is missing two copies of the alpha globin chain. African deletion pattern has one deletion on each chromosome, so no chance of two ppl w/this pattern having a four deletion alpha thal child. Asian pattern has one chromosome carrying both deletions. |
|
|
Term
|
Definition
| 3 deletion alpha thal. Moderate microcytic anemia presenting in infancy. See clusters of HbH (four beta chains) on electrophoresis. Peripheral smear shows target cells and schistocytes |
|
|
Term
|
Definition
| 4 alpha thal. Stillborn, but can be supported by intrauterine transfusion |
|
|
Term
| HbH disease peripheral smear |
|
Definition
| Three deletion alpha thal. Target cells, schistocytes, and HbH upon electrophoresis. Hyperbilirubinemia bc hemolysis is more of a problem here than it is in beta thal |
|
|
Term
| Bilirubin in thalassemia (different!) |
|
Definition
| Alpha has mild hyperbilirubinemia, but beta does not bc hemolysis is not as much of a problem |
|
|
Term
| Three deletion alpha thal treatment |
|
Definition
| Transfusion therapy occasionally may be required (not as profound as homozygous beta thal). Signs of chronic hemolysis manifest- splenomegaly, mild hyperbilirubinemia, jaundice. Not life shortening, unlike homozygous beta thal! |
|
|
Term
|
Definition
| Inhibits the vit k dependent factors, X, IX, VII, II |
|
|
Term
| Defects in primary hemostasis |
|
Definition
| Platelet defects. Onset of bleeding after trauma is immediate. Bleeding in superficial sites- skin, mucous membranes, nose,GI and genitourinary tracts. Physical findings include petechiae and ecchymosis. Family history is AD. Response to tx is immediate and local measures are effective. |
|
|
Term
| Defects in secondary hemostasis |
|
Definition
| Onset of bleeding after trauma is delayed (hrs or days later). Sites of bleeding are deep-joints, muscle, retroperitoneum. Physical findings include hemarthroses and hematomas. Family history is autosomal or x-linked recessive. Therapy requires sustained therapy |
|
|
Term
| At what platelet counta re you at risk for spontaneous bleeding? |
|
Definition
|
|
Term
|
Definition
| New platelets. If you see these in a thrombocytopenic patient, then there is probably a destruction problem |
|
|
Term
|
Definition
| Old platelets. If you see these in a thrombocytopenic patient, it's probably a production problem. |
|
|
Term
| Bleeding time is a measure of... |
|
Definition
| primary hemostasis. Screening test for platelet defects or defects in platelet-endothelial interactions. Von Willebrand's disease or asprin and other anti-platelet drug induced effects |
|
|
Term
|
Definition
| Replaced bleeding time, and is valid in thrombcytopenic patients (as low as 30,000/microliter vs 100,000/microliter as seen in bleeding time). In vitro bleeding time. Measures time it takes for platelets to plug a microscopic hole in a membrane as blood passes through the hole |
|
|
Term
|
Definition
| Measures TF, FVII, FX, FV, Thrombin, and Fibrinogen (extrinsic and common) Measures drops below 40%; fibrinogen deficiency (less than 100mg/dl) will also give abnormal results |
|
|
Term
|
Definition
| Measures Intrinsic and common. FXII, FXI, FIX, FVIII, FX, FV, Thrombin, Fibrinogen |
|
|
Term
|
Definition
| Monitoring pts on coumadin therapy (vit K antagonist), also useful for detecting Vit K deficiency due to other causes, not affected by heparin (PTT used). Normal range varies from hospital to hospital! |
|
|
Term
|
Definition
| (PT of pt/mean pt of normal range)^ISI |
|
|
Term
|
Definition
| 40% of coagulation factors (actually ok) |
|
|
Term
| Increased risk of bleeding occurs at an INR of... |
|
Definition
|
|
Term
| An increased PT time means (3) |
|
Definition
| 1. Liver disease 2. Vit K deficiency 3. Coumadin therapy |
|
|
Term
| an increased aPTT means (4) |
|
Definition
| 1. Coag factor deficiency 2. Fibrinogen deficiency 3. Heparin contamination in sample 4. Inhibitor or antibodies against coag factors (heparin, lupus anticoag, specific factor inhibitors) |
|
|
Term
|
Definition
| Escape of blood outside of vessels into tissue, cavaties, or out of body |
|
|
Term
| Three causes of hemorrhage |
|
Definition
| 1. Vascular diseases (holes in vessels) with rupture or leakage (atherosclerosis, arteritis, aneurysms, polyps, infarcts) 2. Low platelet count (below 10,000) or low platelet function 3. Low coagulation factors (less than 10% activity) or decreased fxn |
|
|
Term
| Petechiae (2 areas for abnormalities) |
|
Definition
| Platelet or capillary fxn caused |
|
|
Term
|
Definition
| Multifactoral hemorrhage into skin |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Color of chronic bleeds/old blood |
|
Definition
| Brown discoloration in skin or maroon paste-like material |
|
|
Term
|
Definition
| Increased amount of blood within the tissues, within the blood vessels. Commonly leads to edema and capillary rupture. Can either be due to increased blood volume due to arteriolar vasodilation (usually physiologic; called hyperemia) or blockage, causing back-up and reduced outflow of blood from a tissue (passive and usually pathologic). Tissues w/acute congestion are red or purple, engorged, swollen, often edematous. Chronic congestion is usually brown and fibrotic. |
|
|
Term
|
Definition
| Active process in which arteriolar dilation leads to increased blood flow. A physiologic, active form of congestion |
|
|
Term
|
Definition
| Active congestion= inflammation, blushing, exercise, sexual arousal |
|
|
Term
| Examples of passive congestion |
|
Definition
| Venous thrombus (local) and congestive heart failure(diffuse). Local congestion will cause blockage upstream: Cirrhosis causes varices in esophagus; thrombus in leg vein causes congestion of foot |
|
|
Term
|
Definition
| Increased water within the tissues, either intra or extracellular, but not in the blood vascular space. Can be secondary to congestion |
|
|
Term
|
Definition
| Hydrothorax; type of edema |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Edema in peritoneal cavity |
|
|
Term
|
Definition
| Widespread edema; subcutaneous tissue swelling |
|
|
Term
|
Definition
| Edema in the brain; intra or extracellular |
|
|
Term
|
Definition
| 1. Venous thrombosis upstream edema 2. CHF 3. Kidney disease (lose protein into urine) 4. Leaky bowel (lose protein into bowel) 5. Liver disease (fail to make proteins and portal hypertension) |
|
|
Term
|
Definition
| Mechanisms and response of cells or tissues to the etiologic agent, whether it is intrinsic (genetic) or extrinsic (acquired). Second step in disease process. Sequence of events from stimulus to disease |
|
|
Term
|
Definition
| Promonitory symptom before recognized as disease |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| example of physiologic and pathologic hypertrophy |
|
Definition
| Physiologic- hypertrophy of uterus in pregnancy (increase in structures in cells) Pathologic: hypertrophy of heart muscle in increased workload due to atherosclerosis or hypertension |
|
|
Term
| Physiologic hyperplasia (2 categories) |
|
Definition
| 1. Increases functional capacity of a tissue when needed; Hormonal hyperplasia (bone marrow hyperplasia, breast in pregnancy) 2. Compensatory hyperplasia increases tissue mass after damage or partial resection(bone marrow hyperplasia in anemia, liver regeneration) |
|
|
Term
| Two examples of pathologic hyperplasia |
|
Definition
| Caused by excessive hormonal stimulation or GFs. Endometrial hyperplasia (caused by increase in estrogen) and Benign Prostatic Hyperplasia (BPH; caused by an increase in androgens). Fertile ground for cancer development, but hyperplasia is controlled by regulatory mechanisms and regress if stimulation is eliminated. Both have increased numbers of glandular cells |
|
|
Term
| Two examples of physiologic atrophy |
|
Definition
| 1. Common in early development (atrophy of thyroglossal duct during fetal development) 2. Loss of endocrine stimulation (atrophy of endometrium, breast, and vagina after menopause due to loss of estrogen stimulation) |
|
|
Term
| Four causes of pathologicic atrophy |
|
Definition
| 1. Decreased workload (atrophy of dissuse) 2. Loss of innervation 3. Diminished blood supply (ischemia; ex-brain atrophy due to narrowed vessels) 4. Inadequate nutrition (muscle wasting/cachexia; chronic inflammatory diseases or cancer) 5. Aging (senile atrophy; atrophy of the brain and heart) 6. Pressure (tissue compression; enlarging brain tumor compressing on brain tissues) |
|
|
Term
| Morphologic changes in irreversible cell injury and necrosis |
|
Definition
| Increased eosinophilia, cytoplasm vacuolation, calcification of the dead cells, nuclear changes: Karyolysis (loss of basophilia of the chromatin), pyknosis (nuclear shrinkage), 3. Karyorrhexis (fragmentation of nucleus) |
|
|
Term
|
Definition
| Nuclear change in cell death/necrosis. Loss of basophilia of the chromatin and degradation of chromatin |
|
|
Term
|
Definition
| Nuclear change in cell death; nuclear shrinkage |
|
|
Term
|
Definition
| Nuclear change in cell death; fragmentation of nucleus |
|
|
Term
|
Definition
| Morphologic changes that follow cell death in living tissue. Necrosis is always a pathologic process. Proteins released into the blood during necrosis are used in diagnosis. Membrane damage leads to leakage of contents, wchi elicits inflammation. Morophologic changes include increased eosinophilia, cytoplasmc vacuolation, and nuclear changes due to DNA breakdown: pyknosis (nuclear shrinkage), karyolysis (degradation of chromatin and loss of basophilia), and karyorrhexis (nuclear fragmentation). Four types are coagulative, liquefactive, caseous, and fat necrosis |
|
|
Term
|
Definition
| Primary pattern is denaturation, but tissue architecture is generally preserved. Usually caused by hypoxic/ischemic injury, but may also be caused by freezing, burns, or chemicals. Ischemia casued by obstruction of a vessel in all areas except brain leads to coagulative necrosis. Localized area of coagulative necrosis=infarct. Clinical findings are pain, loss of cellular and organ fxn (heart failure or arrhythmia), and bleeding (in a GI infarct or due to mucosal damage) |
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Term
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Definition
| Enzyme digestion is primary pattern. Completely digests cells. ex- Brain abscess due to bacterial or fungal infection. Digestion of dead cells changes tissue into a liquid viscous mass. Focal bacterial or fungal infections stimulate accumulation of leukocytes, which release enzymes. Necrotic material=pus. Hypoxic death of CNS cells results in liquefactive mnecrosis. Presents as swelling, redness, fever, pain, and loss of fxn (due to infection that causes inflammation) |
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Term
| Clinical findings of liquefactive necrosis |
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Definition
| Swelling, redness, fever, pain, and loss of fxn due to infection that causes inflammation |
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Term
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Definition
| White gross appearance caused by TB and some fungi and rheumatoid disease. Necrotic area appears as amorphous granular debris enclosed w/in a distinct granuloma. Clinical findings in tuberculosis are caseating granulomas, and in fungal infections, caseating and non-caseating granulomas |
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Term
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Definition
Focal areas of fat destruction resulting from lipase activity. Pancreatic enzymes liquefy the membranes of fat cells in the peritoneum. Lipases split triglycerides into
FAs, which combine w/Ca2+ to produce visible chalky-white areas by saponification. Histologic examination of the necrosis takes the form of foci of shadowy outlines of necrotic fat cells, with basophilic calcium deposits, surrounded by an inflammatory rxn. Causes are trauma/surgery and acute pancreatitis. See foamy macrophages, giant cells, and PMNs. Clinical associations are acute pancreatitis (enzymatic damage), traumatic (pt presents w/pain), and necrosis of subcutaneous tissue (breast mimics cancer). ex- acute pancreatitis- destruction of pancreatic parenchyma by pancreatic lipases |
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Term
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Definition
| Not a distinct pattern of cell death. Refers to a limb that has lost its blood supply and has undergone coagulative necrosis involving multiple tissue planes (if we're talking about dry gangrene). When bacterial infection is superimposed, there is more liquefactive necrosis bc of the action of degradative enzymes in bacteria and leukocytes=wet gangrene |
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Term
| If there is damage to cardiac muscle cells, the enzyme that will be elevated is |
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Definition
|
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Term
| If liver cells are damaged in necrosis, the enzyme that will be elevated in the blood is... |
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Definition
| Alanine transaminase (ALT) |
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Term
| If striated muscle is damaged in cell death/necrosis, the enzyme that will be elevated in the blood is... |
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Definition
|
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Term
| If the exocrine pancreas is damaged in necrosis, the 2 enzymes that will be elevated in the blood are... |
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Definition
|
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Term
| Two types of physiologic apoptosis |
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Definition
| 1. Elimination of unwanted or potentially harmfull cells and old cells (ex-programmed destruction of cells during embryogenesis) 2. Hormone dependent involution in adults (ex- ovarian follicular atresia in menopause, atrophy of prostate after castration, regration of lactating breast after weaning) |
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Term
| Three examples of hormone-dependent involution/apoptosis in adults |
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Definition
| 1. Ovarian follicular atresia in menopause 2. Atrophy of prostate after castration 3. Regration of lactating breast after weaning |
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Term
| Four examples of pathologic apoptosis |
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Definition
| 1. Cell death induced by injurious stimuli (anticancer drugs kill cells) 2. Cell death caused by viral infection (ex- viral hepatitis) 3. Pathologic obstruction in body organs (due to duct obstruction in kidneys, pancreas) 4. Cell death in tumors (during regression) |
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Term
| Celular changes in apoptosis |
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Definition
| Cell destined to die is small, cytoplasm denser, and organelles tightly packed. Chromatin condense and aggregates form under the nuclear membrane. Cytoplasmic blebs and apoptotic bodies form, and there is phagocytosis of apoptotic cells by macrophages. |
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Term
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Definition
| Three things that cause thrombosis: 1. Endothelial injury/vascular wall abnormalities 2. Abnormal blood flow/turbulent or decreased flow 3. Hypercoagulability |
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Term
| HIstology of cross section of DVT |
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Definition
| Inflammation in response to thrombus, and this will lead to some fibrosus. Clot grows cyclically, forming lines of Zahn. White bands-platelet rich. Red bands- RBC and fibrin rich |
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Term
| Who is at high risk for venous thrombosis? AKA acquired hypercoagulable states (6) |
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Definition
| 1. Prolonged bed rest or immobilization 2. Stroke/limb paralysis 3. Tissue damage that releases TF, triggering clotting 4. Cancer (mainly mucin producing adenocarcinomas; Trousseau's is a solid tumor that releases TF) 5. Antiphospholipid antibody syndrome 6. HIT |
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Term
|
Definition
| Solid tumor that releases TF and clotting system is active over a long period of time. Get spontaneous clotting and hypercoagobility, placing the pt at high risk for venous thrombosis. Mucin producing adenocarcinomas |
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Term
| Who is at low risk for venous thrombosis? |
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Definition
| CHF, nephrotic syndrome, obesity, varicose veins, long distance travel, hyperestrogenic states (pregnancy or hormone therapy), OCs, smoking, age |
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Term
|
Definition
| First DVT before 50 yrs of age, recurrent DVT, positive family history. Common causes are mutations in FV (FV Leiden), prothrombin gene, homocystein metabolism, high levels of FVIIIC. Rare causes are ATIII deficiency, PC deficiency, PS deficiency. Very rare are fibrinolysis defects (fibrinogen w/mutation rendering it resistant to fibrinolysis) |
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Term
| Neonatal purpura fulminans |
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Definition
| Homozygous PC deficiency that puts you at a great risk for VTE. Will die if not given PC replacement and anticoagulants |
|
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Term
| Two most common causes of thrombophilia |
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Definition
| 1. Vessel wall problems 2. FV Leiden |
|
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Term
| What tests do you do if a person comes in w/an idiopathic DVT? |
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Definition
| Full thrombophilia diagnostic panel bc you need 2+ risk factors. Test: ATIII, PC, PS, FV Leiden, Prothrombin polymorphism, FVIIIC level, Fasting homocystein level, lupus anticoagulant tests (clotting and immunoassay) |
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Term
|
Definition
| 1. Prophylactic anticoag in high risk pts 2. Heparin followed by coumadin in established DVT/PE 3. Major PE may require fibrinolytic therapy or surgical removal - Long term therapy if there is more than one genetic defect, initial life-threatening thrombosis, cerebral, mesenteric, portal or hepatic vein thrombosis, or two or more spontaneous thrombotic events |
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Term
| Two long term complications of VTE |
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Definition
| 1. High recurrence rates of DVT 2. Post thrombotic syndrome is common even when DVT has been treated. Cause swelling, pain, ulcers. Not preventable, but if you get at it and tx it early, it can be less serious |
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Term
|
Definition
| Complication of DVT. Common even when the DVT has been treated. Swelling, pain, ulcers. NOt preventable, but if you get at it and tx it early, it can be less serious. Mechanism is that the damaged valve wont' fully close and blood flows back down into leg (venous insufficiency). Valves start blowing out and leads to edema and pain and possibly venous ulcers. Venous ulcers are due to stasis from blood backing up. Ulcers are hard to tx bc now the ability of body to repair is decreased |
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Term
|
Definition
| The process by which thrombi are formed. Must be solidified blood (1) within a vessel (2) of a living organ (3) |
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Term
|
Definition
| 1. Stenosis or blockage of an arterial lumen will cause ischemia or infarct 2. Venous occlusion will cause local congestion or edema, possibly PE 3. Left heart valve/chamber thrombi will lead to systemic embolism |
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Term
| 6 things that can happen to a thrombus |
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Definition
| Resolve, propagate, embolize, organize, recanalize, calcify (phlebolith) |
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Term
|
Definition
| End result of clot organization. Ingrowth of capillaries forming channels. Clot won't break apart now bc it has collagen in it |
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Term
|
Definition
| Intravascular, by definition. Arteries, veins, heart chambers, heart valves. Either bland or septic. |
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Term
|
Definition
| A bolus of material which travels through the vascular system. May be gas, liquid, or solid. Most common: thromboembolism. |
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Term
|
Definition
| 1. Gas (air, nitrogen) 2. Liquid (amniotic fluid, contrast materia, fat after soft tissue trauma or fracture, injectables) 3. Solid: Thrombus is most common; also foreign bodies like catheter tips, atheroembolism (plaque broken off vessel wall), bone marrow). *Thromboemboli can get infected. Fat and marrow emboli are microscopic |
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Term
| If a thrombus breaks off from an artery, it will embolize to |
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Definition
|
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Term
|
Definition
| Liquid embolism. MIcroscopic fat globules can be found in circulation and impacted in pulmonary vasculature after fracture or disruption of long bones. Fat and marrow PEs are common after CPR and are probably of no clinical consequence. Occur in 90% of ppl w/fractures, but only 10% have symptoms. Symptoms may be acute shortness of breath, chest Xray showing white lung field. Will see fat in capillaries |
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Term
| Clinical significance of emboli (what three things can they lead to) |
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Definition
| 1. Ischemia 2. INfarction 3. Sepsis (if infected, can spread infection) |
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Term
|
Definition
| Localized area of ischemic necrosis, either caused by occlusion of arterial supply or venous drainagel. Nearly all infarcts result from thrombotic or embolic arterial occlusion. Occasionally caused by vasospasm, hemorrhage into atheromatous plaque, extrinsic vessel contraction, torsion of vessel, traumatic rupture, vascular compromise by edema) |
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Term
|
Definition
| Bland vs septic. Red vs white. Red infarcts are caused by venous occlusions, in loose tissues, in tissues w/dual blood supply, in tissues previously congested by sluggish venous outflow, where flow is reestablished to a site w/previous arterial occlusion and necrosis. White infarcts are caused by arterial occlusion in solid organs (heart, spleen, kidney) or where tissue density limits seeping of blood from adjoining capillary beds into necrotic area. Acute infarcts are poorly defined and slightly hemorrhagic. |
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Term
| 5 causes of red infarcts/where they occur |
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Definition
| 1. Venous occlusions (ovary) 2. In loose tissues (lung) 3. In tissues w/dual blood supply (lung and GI). 4. In tissues previously congested by sluggish venous outflow 5. Where flow is reestablished to a site w/previous arterial occlusion and necrosis |
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Term
| Two causes of white infarcts |
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Definition
| 1. Arterial occlusion in solid organs (heart, spleen, kidney) 2. Where tissue density limits seeping of blood from adjoining capillary beds into necrotic area |
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Term
|
Definition
| If an infarct is caused by a septic embolis or thrombis. Bacteria love infarcts bc PMNs can't survive here. Infected cardiac valve can embolize and cause an infarct, which will become an abscess w/inflammation. Abscess will organize and form a scar |
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Term
| What happens to infarcts over time? |
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Definition
| They heal from the outside and become more shrunken and fibrous. Granulation tissue- healing, old, organized. Becomes a scar. |
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Term
| Clinical significance of infarcts (4 things they lead to) |
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Definition
| 1. Pain 2. Loss of function 3. Hemorrhage 4. Sepsis |
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Term
|
Definition
| Decreased blood flow to an organ or tissue. Often distinguished from infarction clinically. Causes pain, but not tissue death. Reversible. |
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Term
| How do you measure fibrinogen concentration? |
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Definition
| Add a bunch of thrombin to try to induce a clot. This cannot distinguish between hypofibrinogenemia or dysfibrinogenemia. Normal hemostasis maintained until fibrinogen drops below 100mg/dl |
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Term
| If a 50/50 mixing test comes back indicating a deficiency... |
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Definition
| Order individual assay levels. Rule out deficiencies in FVIII, FIX, FXI (we're assuming that there is a normal PT, so couldn't be due to FX, FV, FII or fibrinogen). Deficiencies in FXII, prekallekrein, and kininogen do not usually cause clinically significant bleeding. |
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Term
| If there is no correction with a 50/50 mixing test.. |
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Definition
| Additional testing needs to be done to determine presence of lupus anticoagulant vs specific factor inhibitor |
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Term
|
Definition
| Most frequent cause of increased PTT that does not correct w/50/50 mixing. May also effect PT if really high. Paradoxically associated with thrombosis and not bleeding |
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Term
| How to correct elevated PT and PTT due to coumadin therapy |
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Definition
| 1. Cessation of coumadin (this will increase FII, VII, IX, X, PS and PC) 2. Administration of Vit K 3. Administration of frozen plasma (quick and only temporary correction) |
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Term
| How do you correct elevated PTT due to heparin therapy? |
|
Definition
| 1. Cessation of heparin usage 2. Administration of protamine to neutralize heparin 3. Plasma is not used |
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Term
|
Definition
| Made from fresh frozen plasma. Contains only vWF, FVIII, FXIII, fibrinogen. Used to tx low fibrinogen levels. Not first line therapy for ppl with Hemophilia A or von Willebrand disease |
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Term
| When do you use plasma to correct coagulation factor defects? |
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Definition
| Only when vit K is ineffective or not fast acting enough. Correction of INR w/plasma is only temporary. Do not use when specific coag factor concentrates are available |
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Term
| When to transfuse platelets for thrombocytopenia |
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Definition
| When platelet countn is below 10,000 per microliter, unless febrile or septic (below 20,000). If activately bleeding, or increased risk of bleeding in a non-expandable space, keep it above 50,000 per microliter |
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|
Term
| What three kinds of thrombocytopenia do you not transfuse for? |
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Definition
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Term
| Liver disease and hemostasis |
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Definition
| Most common acquired disorder of both primary and secondary hemostasis. Increased bleeding also due to formation of varices from portal hypertension. Liver isn't making enough coag factors (leads to bleeding), DIC (leads to microthrombi and bleeding), systemic fibrinolysis (due to inefficient clearance of TPA and reduced alpha-2 antiplasmin release), and thrombocytopenia (reduced thrombopoietin, splenomegaly, immune mediated platelet destruction) and platelet function disorders (reduced activation of platelets). |
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Term
| Disseminated Intravascular Coagulation |
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Definition
| Thrombohemorrhagic disorder characterized by the excessive activation of coagulation, which leads to the formation of thrombi in microvasculature of the body. Secondary complication of many different disorders, including liver diseases. As a consequence of the thrombotic diathesis there is consumption of platelets, fibrin, and coagulation factors and, secondarily, activation of fibrinolysis. Can present w/signs and symptoms relating to the tissue hypoxia and infarction caused by the myriad microthrombi, with hemorrhage caused by the depletion of factors required for hemostasis and the activation of fibrinolytic mechanisms; or both. The two major mechanisms that trigger DIC are release of TF or thromboplastic substances into the circulation, and widespread injury to endothelial cells. Most likely associated with obstetric complications, malignant neoplasms, sepsis, and major trauma. Widespread deposition of fibrin within the microcirculation leads to ischemia of the more severely affected or more vulnerable organs and a microangiopathic hemolytic anemia, which results from the fragmentation of red cells as they squeeze through the narrowed microvasculature. The consumption of platelets and clotting factors and the activatio of plasminogen leads to a hemorrhagic diathesis. Plasmin cleaves fibrin and digests FV and FVIII, thereby reducing their concentration further. Impossible to detail the possible clinical presentation, but a few common pattens are microangiopathic hemolytic anemia; dyspnea, cyanosis, and respiratory failure, acute renal failure, shock. When associated with an obstetric complication or major trauma, it is dominated by a bleeding diathesis. In chronic DIC, such as in Trousseau's syndrome, you often have thrombotic complications. Diagnosis is based on clinical observation and laboratory studies, including decreased fibrinogen, platelets, and increased PT and PTT. Tx by removing the inciting cause. Leads to microcytic anemia with high RDW. If the pt is thrombosing, give heparin and ATIII and PC |
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Term
| What are the secondary coagulation problems associated w/liver disease? |
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Definition
| Decreased coag factor synthesis and Vit K deficiency due to malnourishment. Dysfibrinogenemia preventing clotting, and systemic fibrinolysis. Fibrinolysis is due to ineffective clearance of tissue plasminogen activator and reduced alpha-2-antiplasmin release. DIC also plays a role, using up clotting factors and fibrinogen |
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Term
| What causes systemic fibrinolysis in liver disease? (2) |
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Definition
| Inefficient clearance of TPA leading to increased plasmin, which increases fibrinolysis. Reduced alpha-2-antiplasmin release=loss of plasmin inhibitor leads to increased plasmin that keeps breaking up clots |
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Term
| Primary coagulation problem in liver disease (4) |
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Definition
| 1. Reduced thrombopoietin release leads to thrombocytopenia 2. Reduction in platelet activation due to failure to clear inhibitors 3. Splenomegaly leads to platelet sequestration, short platelet life, and decrease in platelet number |
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Term
|
Definition
| May lead to decreased fibrinogen and increased FDP dimers in addition to increased PT, PTT, and decreased platelet from liver disease. Procoagulants are released from sick hepatocytes, and there are endotoxins in the portal circulation that are not being cleared by the liver. Liver also fails to clear activated clotting factors. Reduced ATIII and PC (this increases thrombosis). Elevated cytokines, sepsis, peritoneovenous shunts |
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Term
|
Definition
| Mainly remove inciting cause. Plasma if bleeding, heparin, ATIII and PC if clotting |
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Term
| Lab values for liver disease |
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Definition
| Macrocytic anemia with normal RDW and low reticulocytes (production problem). High PT, PTT, thrombocytopenia, high PFA. Due to DIC may have decreased fibrinogen and high FDP dimer |
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Term
| Lab results for hemophilia |
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Definition
| PT and PFA are normal, PTT is high. 50/50 mixing corrects |
|
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Term
| Normal PTT and high PT suggests |
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Definition
|
|
Term
| How females w/hemophilia A or B can be symptomatic (3) |
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Definition
| 1. Homozygosity (mother was carrier, father had it) 2. Lyonization/inactivation of healthy allele in carriers 3. Hemizygosity of X chromosome (Turners: XO) |
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Term
|
Definition
| 1. Recombinant factor 2. Purified monoclonal antibody 3. Cryo if its FVIII deficiency (cryo contains FVIII, XIII, vWF and Fibrinogen) 3/4. Plasma *If it is a mouth or GI bleed, drugs that block fibrinolysis can be used initially prior to factor replacement. Use FVII to bypass inhibitors |
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Term
|
Definition
| Can occur in a pt with normal expression of FVIII or FIX, but who develop an autoantibody against it |
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|
Term
|
Definition
| High PTT, normal PT, high PFA, normal platelet count |
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Term
|
Definition
| Shows up as high PTT, normal PT, high PFA, normal platelets. AD mutation on chromosome 12, leading to decreased vWF and subsequent decrease in FVIII. Wide spectrum of bleeding symptoms and may present at any age. |
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Term
|
Definition
| 1. Platelet-subendothelial binding (vWF binds platelet GP-Ib and to subendothelial collagen, adhering platelets to damaged vessel wall 2. Platelet-platelet binding: vWF binds to platelet receptor GIb in areas of high shearing stress, causing platelet aggregation 3. Carries FVIII in the plasma, protecting it from proteolysis |
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Term
| Ristocetin cofactor activity |
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Definition
| Demonstrates vWF activity. Ristoceitin binds to vWF on platelets and causes them to aggregate; stimulates vWF-dependent aggregation. Ristoceitin-induced platelet aggregation is reduced in Type 1 vWD and Type 3 vWD (quantitative deficiencies of vWF), Type 2a (qualitative deficiency of vWF), and is increased in Type 2b |
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Term
|
Definition
| Partial quantitative deficiency of vWF. Most common. Decreased ristoceitin-induced platelet aggregation. Fewer vWM multimers, but same low vs high molecular weight distribution. Tx by first choice giving DDAVP, a synthetic analogue of ADH that stimulates release of remaining vWF from endothelial stores. Second choice is affinity purified vWF (no recombinant available); third choice is cryo |
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Term
| How do you tx type 1 vWD? |
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Definition
| 1. DDAVP (synthetic analogue of ADH that stimulates release of remaining vWF from endothelial stores) 2. Affinity purified vWF 3. Cryo |
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Term
|
Definition
| Qualitative deficiency of vWF. Reduced ristoceitin-induced platelet aggregation. Lose more high molecular weight multimers. To tx, sometimes use DDAVP, or affinity purified vWF |
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Term
| How do you tx type 2a vWD? |
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Definition
| DDAVP sometimes tried, affinity purified vWF |
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Term
|
Definition
| Qualitative deficiency of vWF. Ristoceitin-induced platelet aggregation is increased. Decreased amount of vWM multimers but soame low vs high molecular weight distribution. Tx- avoid DDAVP bc there is a theoretical thrombocytosis/thrombocytopenia risk; affinity purified vWF |
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Term
| How do you tx type 2b vWD? |
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Definition
| Avoid DDAVP bc there is a thrombocytosis/thrombocytopenia risk (increased vWF activity demonstrated by increased ristoceitin-induced platelet aggregation) |
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Term
|
Definition
| Qualitative deficiency of vWF. Decreased platelet dependent function not caused by absence of high MW multimers, like it is in type 2A (which has loss of high molecular weight multimers and reduced ristoceitin-induced platelet aggregation) |
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|
Term
|
Definition
| Qualitative deficiency of vWF. Decreased platelet dependent function not caused by absence of high MW multimers, like it is in type 2A (which has loss of high molecular weight multimers and reduced ristoceitin-induced platelet aggregation) |
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Term
|
Definition
| Qualitative deficiency of vWF. Markedly decreased affinity for FVIII |
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|
Term
|
Definition
| Nearly complete deficiency of vWF. Ristoceitin-induced platelet aggregation is nearly absent. Very few vWM multimers are seen. Tx- affinity purified vWF. DDAVP has no value |
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|
Term
| How do you tx type 3 vWD? |
|
Definition
| Affinnity purified vWF. DDAVP has no value. |
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Term
|
Definition
| Qualitatibe defect in platelet GPIb-IX receptor. This receptor interacts w/vWF in subendothelium to cause platelet aggregation and adhesion. Platelet type vWD has this mutation and causes increased affinity for vWF |
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Term
|
Definition
| Increased PT and normal PTT. Rare congenitally, but Coumadin induced is not rare. FVII is the first factor to disappear w/Coumadin or Vit K deficiency |
|
|
Term
|
Definition
| Increased PTT and normal PT. No increased risk of bleeding, no factor replacement required, even in the bleeding patient. |
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|
Term
|
Definition
| Increased PTT and normal PT. Found in 8% of Ashkenazi Jews. No increased risk of bleeding until factor level is found below 15-20%. Tx is plasma transfusion (no recombinant or purified form and is not found in cryo) |
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Term
|
Definition
| Plasma transfusion (there is no recombinant factor or purified form) |
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|
Term
|
Definition
| Increased PTT and PT. No increased risk of bleeding until level is below 10-20%. Can be an acquired deficiency in amyloidosis pts. Pt can be refractory to replacement therapy, as FX is rapidly removed from circulation by amyloid fibrils. Tx- plasma transfusion (no recombinant or purified form) |
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|
Term
|
Definition
| Plasma transfusion (no recombinant or purified form). Can be hard to tx in amyloidosis pts (acquired deficiency of FX in these pts) bc FX is rapidly removed from circulation by amyloid fibrils |
|
|
Term
| What three things can cause fibrinogen deficiency, and what do labs look like and how do you tx? |
|
Definition
| 1. Diutional coagulopathy 2. Dysfibrinognemia 3. DIC (2 and three are found in liver disease) Normal PTT and PT unless fibrinogen falls below 100mg/dl, when both will increase. Tx- cryo |
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|
Term
| How do you tx fibrinogen deficiency? |
|
Definition
|
|
Term
|
Definition
| Normal PTT and PT. FXIII crosslinks fibrin clot and incorporates antiplasmin, preventing rapid lysis of clots after formation. Presents w/umbilical cord bleeding, intracranial hemorrhage, superficial bruising, fetal loss, or poor wound healing. Try to dissolve clot in uric acid, and it should not come apart- if it does, it is missing fibrin cross linkns. Tx- FXIII has a long half-life, so only occasional plasma transfusions are needed |
|
|
Term
| 3 Thrombocytopenia types caused by primary immune destruction of platelets |
|
Definition
| 1. ITP 2. Post-transfusion purpura 3. Neonatal alloimmune thrombocytopenia |
|
|
Term
| 6 Types of thrombocytopenia caused by secondary immune destruction |
|
Definition
| Infection, systemic lupus erythematosus, B-cell lymphoid neoplasms, chronic lymphocytic leukemia, Hodgkin disease, HIV, HIT |
|
|
Term
| 6 non-immune causes of destruction/sequestration thrombocytopenia |
|
Definition
| 1. DIC 2. Hypersplenism 3. Preeclampsia-eclampsia leading to HELLP 4. Malignant hypertension 5. Severe vasculitis 6. TTP |
|
|
Term
| 5 causes of decreased platelet production causing thrombocytopenia |
|
Definition
| 1. Aplastic anemia/Fanconi's pancytopenia 2. Marrow infiltrative processes (Malignancies that grow into marrow, myelofibrosis, osteopetrosis, infection) 3. Amegakaryocytic thrombocytopenia 4. Nutritional deficiencies 5. Drug or radiation-induced |
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|
Term
| Hereditary thrombocytopenias |
|
Definition
| Often mild or asymptomatic, although there are some exceptions where thrombocytopenia is severe. ex- amegakaryocytic thrombocytopenia (inherited decrease in megakaryocytes) |
|
|
Term
| Two miscellaneous diseases that can cause thrombocytopenia |
|
Definition
| Liver disease and renal disease. In liver disease, you have decreased thrombopoietin, decreased platelet activation, splenomegaly and platelet sequestration, and immune-mediated platelet destruction |
|
|
Term
| 4 marrow infiltrative processes that can cause production thrombocytopenia |
|
Definition
| 1. malignancies that grow into marrow 2. Myelofibrosis 3. Osteofibrosis (marrow doesn't stay in bones) 4. Infection |
|
|
Term
| Immune Thrombocytopenic purpura |
|
Definition
| Low PT and increased PFA. Labs show increased megakaryocytes. Defect- anti-GpIIb/IIIa antibodies lead to peripheral platelet destruction. Looks like a bleeding disorder; increased platelet destruction; lg platelets. Childhood is acute and follows viral infections and usually spontaneously resolves. Adult form may last indefinitely. Autoantibodies against platelet GPIIb-IIIa (fibrinogen) and IbIX (vWF) receptors. |
|
|
Term
| Childhood (acute) immune thrombocytopenic purpura |
|
Definition
| Autoantibodies against GPIIb-IIIa (fibrinogen) and GPIb-IX (vWF) receptors on platelets. Childhood one occurs usually after viral infections, lasts 6-12 months with spontaneous remission in 80%. Boys=girls. Usually btw 3-5yrs. Steroid therapy if severe. 20% develop into chronic form of ITP (those who did not have a viral infection). Low platelet count and increased BT. Labs show increased megakaryocytes |
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|
Term
| Adult (chronic) Immune Thrombocytopenic Purpura |
|
Definition
| Three times more women than men. Melena, increased menstrual flow, nose and gum bleeds, easy bleeding, rarely a sudden onset of heavy bleeding. Its destruction, so see lg platelets in smear. Tx- glucocorticoids to inhibit phagocytic activity or drive down Ab production, IVIG (by giving Abs from a healthy donor, drive down endogenous production), anti-RH IG (save platelets at the expense of red cells), Rituximab (monoclonal antibody against B-cells), splenectomy (spleen removes platelets), chemo. Low PC and high PFA. Labs show increased megakaryocytes |
|
|
Term
|
Definition
| Monoclonal antibody against B-cells. Given for adult/chronic immune thrombocytopenic purpura |
|
|
Term
| Systemic lupus erythematosus |
|
Definition
| Autoimmune disease over which thrombocytopenia may preside. type of secondary ITP (autoantibodies against platelets lead to destruction and thrombocytopenia) |
|
|
Term
| Chronic lymphocytic leukemia |
|
Definition
| Type of secondary ITP that causes thrombocytopenia and platelet destruction. 2% of chronic lymphocytic leukemia pts have an autoantibody produced by a B-cell clone. |
|
|
Term
|
Definition
| 1% develop secondary ITP (autoimmune destruction of platelets->thrombocytopenia) |
|
|
Term
|
Definition
| Thrombocytopenia (secondary ITP; autoantibodies against platelets) is most common hematologic manifestation of HIV |
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Term
| Thrombotic thrombocytopenic purpura |
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Definition
| TTP. Decreased platelet survival. Low PC and increased PFA. Labs show high LDH. In kids, either hemolytic-uremic syndrome (bloody diarrhea Ecoli, renal failure, no neurologic symptoms) or idipathic (without renal failure or bloody diarrhea). TTP in adults is idiopathic (with or without acute renal failure), preg associated, or drug associated. TTP is caused by formation of ultra-large vWF ultimers that keep binding platelets due to deficiency in metalloprotease that cleaves vWF. Normal PT and PTT, decreased platelets due to sequestration, microcytic anemia with high RDW. Thrombocytopenia, hemolysis, schistocytosis. ReNeurologic abnormalities, weakness, abdominal symptoms, low grade fever (high grade rules for sepsis and against TTP). 90% mortality w/o plasma exchange (except in kid's hemolytic-uremic syndrome/Ecoli bc this doesn't require plasma exchange) |
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Term
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Definition
| Plasma exchange to get rid of ultra-lg vWF complexes. 90% mortality w/o. Don't need to do plasma exahange in kid's hemolytic-uremic syndrome (bloody diarrhea w/Ecoli and acute renal failure). |
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Term
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Definition
| 1. Hemolytic-uremic syndrome: Bloody diarrhea caused by Ecoli w/acute renal failure. Don't need to do plasma exchange. Distinguished from idiopathic TTP by absence of neurologic symptoms, the prominence of acute renal failure, and its frequent occurrence in kids. 2. Idiopathic TTP w/o acute renal failure (see neurologic symptoms, bloody diarrhea rare; do plasma exchange) |
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Term
| Hemolytic-uremic syndrome |
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Definition
| One of two types of TTP in kids. Normal PT and PTT, low platelets, microcytic anemia w/high RDW. Bloody diarrhea caused by Ecoli w/acute renal failure. Distinguished from idiopathic TTP by absence of neurologic symptoms. Don't need to do plasma exchange |
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Term
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Definition
| 1. Idiopathic TTP with or w/o acute renal failure 2. Pregnancy associated (may be unable to distinguish from preeclampsia-eclampsia HELLP syndrome) 3. Drug associated: Immune mediated (quinine, ticlopidine, clopidogrel), dose related drug toxicity (mitomycin C, cyclosporine, FK506) |
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Term
| Quinine, ticlopidine, clopidogrel, mitomycin C, cyclosporine, FK506 |
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Definition
| Drugs associated with TTP in adults (normal PT and PTT, low platelets and microcytic anemia w/high RDW) |
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Term
| Preeclampsia-eclampsia leading to HELLP |
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Definition
| HELLP-hemolytic anemia with elevated LFTs and low platelet count). Low platelets, microcytic, hemolytic anemia w/high RDW and schistocytes. Should resolve upon delivery |
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Term
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Definition
| Normal platelet count but decreased PFA. Inhibits aggregation but not adhesion. Cyclooxygenase 1 is permanently inhibited/acetylated by aspirin. This impairs the synthesis of thromboxane A2, whcih has potent platelet-aggregating activity. |
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Term
| Glanzmann's thrombasthenia |
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Definition
| Poor clot retraction. GIIb/IIIa deficiency prevents platelets from binding fibrinogen. AR. Platelets fail to respond to ADP, collagen, epinephrine, or thrombin bc of deficiency or dysfunction of GPIIb-IIIa |
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Term
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Definition
| Giant platelet syndrome due to GPIb deficiency, which is responsible for binding vWF in the subendothelial ECM. Bleeding results from defective adhesion. AR |
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Term
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Definition
| Platelet fxn disorders that result from defective release of certain mediators of platelet activation, such as thromboxanes and granule-bound ADP. Cause bleeding |
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Term
| 4 times you see basophilic stippling |
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Definition
| Baste the ox tail. Thalassemias, anemia of chronic disease, iron deficiency, lead poisoning |
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Term
| 4 times you see target cells |
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Definition
| HALT said the hunter to his target. HbC disease, Asplenia, Liver disease, Thalassemia |
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Term
| Two times you see Heinz bodies |
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Definition
| Alpha thal and G6PD deficiency. Oxidation from iron from ferrous to ferric form leads to denatured hb precipitation and damage to RBC membrane. Leads to formation of bite cells |
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Term
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Definition
| Basophilic nuclear remnants found in RBCs. Seen in pts with functional hyposplenia or asplenia |
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Term
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Definition
| Defect in heme synthesis. Heredeitary- X-linked defect in delta-aminolevulinic acid synthase gene. Tx- pyridoxine (B6) therapy. Reversible etiologies- alcohol or lead. Increased iron, normal TIBC, increased ferritin. Ringed sideroblasts w/iron-laden mitochondria. |
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Term
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Definition
| 1. Neurologic 2. Renal 3. Low grade fever 4. Throbocytopenia 5. Microangiopathic hemolytic anemia |
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Term
| Which three platelet disorders have a low PC and a increased PFA? |
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Definition
| Bernard-soulier (defect in Gp1b/platelet-collagen adhesion) 2. ITP (anti GPIIb/IIIa antibodies leads to peripheral platelet destruction) 3. TTP (lg vWF multimers leads to platelet aggregation and thrombosis) |
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Term
| Labs for Glanzmann's thrombasthenia |
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Definition
| No decrease in platelet count but an increase in PFA. Blood smear shows no platelet clumping. GPIIb/IIIa is low- defect in platelet-platelet aggregation |
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Term
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Definition
| Inherited deficiency of ATIII; reduced increase in PTT after administration of heparin. Hereditary thrombosis syndrome leading to hypercoagulability. ATIII irreversibly inhibits FIIa, FXa, FIXa in solution , and FVIIa when in complex w/TF. |
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Term
| Protein C or S deficiency |
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Definition
| hereditary thrombosis syndrome leading to hypercoagulability. Decreased ability to inactivate FV and FVIII. Increased risk of hemorrhagic skin necrosis following administration of warfarin. |
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Term
| Prothrombin gene mutation |
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Definition
| Hereditary thrombosis syndrome leading to hypercoagulability. Mutation in 3'UTR associated w/venous clots |
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Term
| High PTT, Normal PT, 50/50 mixing doesn’t correct with thrombosis |
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Definition
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Term
| High PTT, Normal PT, 50/50 mixing doesn’t correct with bleeding |
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Definition
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Term
| High PTT, High PT, Low Platelet Count, High PFA (2) |
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Definition
- Liver disease: Bleeding and microthrombi formation. Macrocytic anemia with high RDW and low retics.
- DIC: Microcytic anemia w/high RDW and high retics |
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Term
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Definition
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Term
| High PTT, Normal PT, Normal PFA, 50/50 mixing corrects (three things) |
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Definition
- Hemophilia A or B. May be anemic due to blood loss.
- Too much Heparin |
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Term
| High PTT and PT, Normal platelet and PFA (6 things) |
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Definition
- Fibrinogen deficiency
- FXa deficiency
- FIIa deficiency
- FVa deficiency
- Too much Coumadin/Warfarin
- Vit K deficiency |
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Term
| High PTT, Normal PT, Normal Platelet and High PFA |
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Definition
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Term
| Normal PTT, Normal PT, Normal Platelet and Normal PFA but bleeding |
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Definition
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Term
Normal PTT, Normal PT, Low Platelet, Increased PFA
(3) |
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Definition
- Thrombotic thrombocytopenia purpura; microcytic anemia w/high RDW
- Bernard-Soulier Disease
- Idiopathic thrombocytopenic purpura; labs show increased megakaryocytes |
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Term
| Normal PTT, Normal PT, Normal Platelet, Increased PFA |
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Definition
| - Glanzmann’s thrombasthenia; lab shows no platelet clumping |
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Term
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Definition
| Heparin binds ATIII and increases its activity. It is an indirect inhibitor of Xa and IIa and a little bit of IX. Larger heparin chains can bind thrombin directly. Metabolized by the liver and excreted in the urine. Does not cross the placenta, so is used in pregnancy. Administered IV or subcutaneous. Half-life is highly variable due to heparin-binding proteins (when sicker, the half life decreases). Measure it by PTT. Requires frequent monitoring and dose adjustments |
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Term
| Metabolism of unfractionated heparin |
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Definition
| Metabolized by the liver and excreted in the urine. Does not cross placenta, so used in pregnancy. Short, variable half-life |
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Term
| How is unfractionated heparin administered? |
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Definition
| IV (continuous infusion) or subcutaneous (LMW hep is only available subcut). Highly protein and cell bound, and you have dose dependent absorption from subcut injection sites. 1/2 life, within and between pts is highly variable due to heparin-binding proteins. Shorter halflife in sicker ppl and those w/lg thrombi (average is 90min). Monitor closely by PTT (monitoring in LMWH is unnecessary bc it is in a strict linear relationship w/FXa unless light, pregnant, or in renal failure). |
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Term
| Half-life of unfractionated heparin |
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Definition
| Short and variable btw ppl and within (sick, shorter half life still). Must be closely monitored. LMWH have 2-4 times longer half-life and can be administered subcutaneously and without laboratory monitoring |
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Term
| Clinical use of unfractionated heparin |
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Definition
| Immediate anticoagulant for PE, stroke, acute coronary syndrome (unstable angina or myocardial infarction), DVT. Used during pregnancy bc it does not cross placenta; follow PTT. Extracorporeal circulation-dialysis, bypass. Percutaneous vascular interventions (angioplasty and stents) |
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Term
| Unfractionated heparin adverse effects |
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Definition
| Mainly bleeding that increases w/other drugs that affect coag or platelet function, increases w/invasive procedures, and increased w/renal and liver failure. HIT. Tx of heparin related bleeding complications-immediate discontinuation and protamine (heparin antagonist)- highly basic protein that binds heparin to inactivate it. It also impairs bone formation and enhances bone absorption-osteopenia with long-term use (especially during pregnancy) and thrombocytopenia (2 types). |
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Term
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Definition
| Heparin binds to platelets, causing autoantibody production that destroys platelets and overactivates the remaining ones, resulting in a thrombocytopenic, hypercoagulable state. Two types. Type 1-benign drop up to 20%; reversible stopping Type 2- immunological rxn consisting of antibody response to heparin-platelet factor 4 complexes. Causes platelet aggregation, activation, and thrombosis, not bleeding. |
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Term
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Definition
| Heparin binds to platelets, causing autoantibody production that destroys platelets and overactivates the remaining ones resulting in a thrombocytopenic, hypercoagulable state. PF4 is released from alpha granules of activated platelets and promotes blood coag. Heparin binds PF4, and for some reason, this stimulates production of IgGs against heparin bound to PF4. IgG complexes w/heparin and PF4 in plasma, and the tail of IgG then binds the platelet. This triggers platelet removal by splenic macrophages, as well as platelet activation and aggregation, which leads to the formation of microparticles and thrombosis. |
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Term
| clinical sequelae of HIT (a few days later) 5 |
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Definition
| 1. Venous thrombosis in 50% (DVT with venous limb gangrene or at site of a central line), pulmonary embolism, cerebral vein thrombosis and adrenal infarction 2. Arterial (lower limb arteries usually, MI/stroke) 3. Heparin induced skin lesions at heparin injection sites 4. Acute systemic rxns after IV heparin bolus (inflammatory symptoms, cardiorespiratory symptoms, nausea, diarrhea) 5. Adrenal necrosis/infarct |
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Term
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Definition
| ex- enoxaparin. Act more on Xa, have better bioavailability and 2-4 times longer half-life. Can be administered subcutaneously and without laboratory monitoring. They are not easily reversible. Ultra-low molecular weight=pentasaccharide=fondaparinux. Mechanism of inhibition is indirect (through antithrombin). Conformational change and interaction w/anti-thrombin favors binding of FXa over all other ATIII substrates. Pentasaccharide inhibits FXa only. |
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Term
| Metabolism/excretion of LMW Heparin |
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Definition
| Binds less to plasma proteins and cells than unfractionated heparin. Longer 1/2 life. Significant excretion in the kidneys, requiring increased monitoring w/renal failure. More bioavailable. Administration is only subcutaneous (no IV or oral formulations; unfractionated hep is IV or subcut). Can be administered w/o monitoring, unless you're light, pregnant, or in renal failure. The effect of LMWH on FXa activity is linearly related to dose administered |
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Term
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Definition
| Bleeding. Reversal of bleeding not effective w/protamine. Less documented HIT. Osteoporosis uncommon. Can be administered out-pt bc of subcut!! |
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Term
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Definition
| Interferes w/normal synthesis and gamma-carboxylation of vit K-dependent clotting factors II, VII, IX, X, and protein C and S. Metabolized by the cytochrome P-450 pathway. In laboratory assay, has an effect on EXtrinsic pathway and high PT (the EX-PresidenT went to WARfarin). Long half-life.Blocks VitK epoxide reductase, one of the 2 enzymes needed to reduce Vit K, which is needed to carboxylate Gla residues. No carboxylation leads to no GLA, and no binding of factors to membrane. |
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Term
| Warfarin metabolism and excretion |
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Definition
| Metabolized by P450 detoxification system of the liver. Genetic polymorphisms of the CYP 2C9 enzyme leads to impaired metabolism of warfarin and may require doses of drug substantiallly less than the wild-type enzyme. Extensively bound by plasma proteins- drugs that alter protein binding or affect the liver P450 system may potentiate or inhibit the activity of warfarin. |
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Term
| Clinical use of Warfarin/Coumadin |
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Definition
| Chronic anticoagulation. Not used in pregnant women (bc it can cross placenta, unlike heparin). Follow PT/INR values. Mechanical valves and chronic atrial fibrillation for stroke and thromboembolus prevention. Venous thrombosus tx and prevention |
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Term
| Administration of Warfarin |
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Definition
| Oral. Availability near 100%. Monitor w/lab PT/INR. Narrow therapeutic window. Monitoring is critical to safety and efficacy. Target range depends on indication. |
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Term
| What increases the INR in Warfarin? |
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Definition
| Tons of drug interactions. Displacement from plasma albumin (cotrimoxazole, sulfonamides), alcohol and liver disease, anticoagulents/platelet inhibitors |
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Term
| What two things decrease INR in Warfarin? |
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Definition
| Cholestramine (decreased absorption), increases in liver metabolism (barbituates decrease Warfarin's effects) |
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Term
| Adverse effects of Warfarin |
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Definition
| Bleeding, drug interactions, tissue necrosis due to severe decreases in PC and PS, allergy, teratogenic |
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Term
| contraindications to Warfarin |
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Definition
| Pregnancy, situations where risk of hemorrhage is greater than the potential clinical benefits (uncontrolled alcohol/drug abuse, unsupervised dementia/psychosis, inability to monitor routinely, high risk behaviors) |
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Term
| Three direct thrombin inhibitors |
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Definition
| Argatroban, Bivalirudin, Lepirudin. All directly inhibit thrombin at its active site. All administered via IV. Dosing and dose adjustment is even more complex than Warfarin. Always just use for short duration, inpatient. Adverse effects-bleeding. |
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Term
| 4 toxicological relevant metals |
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Definition
| Cd (Itai-Itai-Disease), Hg (Minamata-Disease), As (Black-Foot-Disease), Pb (Plumbism). These serve no purpose in the human body |
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Term
| Organic or ionic metals more toxic? |
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Definition
| Organic bc they're lipophilic and can enter cell barriers and in turn the food chain more easily. |
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Term
| Three ways that heavy metals are organ specific |
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Definition
| 1. Using transport carriers by mimicking essential ions 2. Bind at peptides which are incorporated into certain cells 3. Bind to Cys-rich proteins (metallothionines are 30% Cys) |
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Term
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Definition
| Complex, multi-step processes. Metal ions act as conspirators w/other biochemical events. Can bind to DNA, create a ROS, catalyze the hydroxylation of DNA, binding to DNA polymerase, DNA repair mechanisms, transcription of proto-oncogenes, signal transduction (Cd in IP3-Ca-PKC cascade) |
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Term
| Which heavy metals are carcinogens? |
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Definition
| Arsenic and cadmium, and maybe lead |
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Term
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Definition
| LEAD. Lead Lines on gingivae (Burton's lines) and on epiphyses of long bones on x-ray. Encephalopathy and Erythrocyte basophilic stippling. Abdominal colic and sideroblastic Anemia. Drops-wrist and foot. Dimercaprol and eDta are first line tx; Succimer for kids. know GI "lead colic"; pain, vomiting constipation); PNS "lead palsy" (muscle weakness, fatigue, tremors, paralysis), CNS (lead encephalopathy; delayed mental growth, can lead to retardation). Bone is largest repository- inhibits osteocalcin (Ca binding protein). Hematopoietic system- interferes with heme synthesis at delta aminolevulinic acid dehydratase and ferrocheletase. |
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Term
| Delta-amino levulinic acid and coproporphyrinogen III and protoporphyrin |
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Definition
| Two urine markers for lead exposure- coproporphyrinogen III and delta-aminolevulinic acid. These build up. Three steps are blocked. The last step in heme synthesis, iron addition by ferrochelatase, is also blocked, and this leads to protoporphyrin accumulation in the blood |
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Term
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Definition
| Like lead, it is a neurotoxin, and adults and kids are effected the same. At the lowest concentrations, they develop tremor freq, EEG changes and decreased verbal intelligence. 1/2 of the mercury in the environment is not mman made. Lots from old car airbag switches, coal, and waste combustion. We are exposed to elemental mercury, divalent mercury, ethyl mercury (thimerosal), and methyl mercury, in this order of toxicity. |
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Term
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Definition
| HgO. 80% retention when inhaled. Proximal toxin is Hg2+. Mainly deposited in the kidney. Partially reversible CNS symptoms (Mad Hatter Syndrome). Associated w/degenerative diseases, such as Alzheimer. Hg0 is lipophilic, and can pass into the blood and brain. In blood or brain, can be converted to ionic, toxic form. 80% of mercury vapor is absorbed to the bloodstream. Mercury vapor is poorly absorbed by GI tract, skin absorption insignificant. Mercury vapor is oxidized to Hg2+ and accumulates in the kidney. While Hgo readily crosses membranes, Hg2+ does not. Clinical signs- tremor, erethism, memory deficit, irritability, decreased conduction velocity, nephrotoxicity, immunotoxicity. Most are reversible in a few months. |
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Term
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Definition
| Most toxic form of mercury. Biologically magnified in aquatic food chains. Hg2+ is converted to this by bacteria. Methylmercury is able to pass into the brain and placenta. 95% of methymercury is absorbed through the GI tract, and because it is lipophilic, it rapidly distributes to most compartments of the body readily crossing the placenta and BBB. Like lead, the brain-mercury connection is strong. Signs of exposure are paresthesia, disarthria, sensory deficit, cerebellar ataxia, cortical visual constriction, and attention deficit in adults or young children. In prenatal/perinatal, get unspecific cerebal palsy, MR, seizures, blindness, quadriplegia. |
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Term
| Mechanisms of methylmercury toxicity |
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Definition
| Binds SH groups and interferes w/calcium homeostasis, protein phosphorylation, ROS, cell cycle control, protein synthesis, and MT assembly. Extremely high thiol affinity. MeHg is taken into the cells by LAT1 (a large, neutral AA transporter), as it mimics Methionine (gets incorporated into methionine). Also, MeHg may be able to simply diffuse accross lipid bilayers. |
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Term
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Definition
| Ethylmercury. Highly effective fungicide found in vaccines and tinctures. More toxic to kidney and less toxic to CNS when compared to methylmercury. Possible connection to autism. |
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Term
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Definition
| Worse than lead. Found all over, especially in root plants and leafy veggies. Also in mineral mining, Ni/Cd batteries, buring fossil fuels, cigarrettes. In contrast to Pb and Hg, Cd is easily absorbed. Most accumulates in liver(where it binds SH containing metallothionines for transport in the blood) and kidney (where it is converted from metallothionine-Cd to its toxic form). Cd's half-life is longer than lead. Interferes with calcium uptake into epithelial cells in the GI tract. Primarily a respiratory carcinogen (oral exposure is not showing much effect) |
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Term
| Cadmium mechanism of toxicity |
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Definition
| Cd loves binding to SH groups. Liver uses this to detoxify metals. Metallothionines are expressed (have high numbers of SH residues) and they gobble up Cd. Md-Metallothionine is released into the blood, where it eventually enters the kidney. Once in renal cells, lysosomes chew up Cd-Met and this is where they do damage. Converted to toxic form here. |
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Term
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Definition
| Inhalation is linked to respiratory tract cancer. Probable human carcinogen |
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Term
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Definition
| Not a heavy metal, but has metallic properties and a metallic and nonmetallic form. Elemental iron is not toxic, but AsIII and AsV are, and AsIII is most toxic. Signs of as poisoning are nausea, vomiting, rice water stools, garlic breath. Mees lines (hyperpigmentation and keratosis on palms) and causes cancers of skin, lung, liver, and bladder. Most comes from drinking contaminated water an in wood preservatives. Three common forms are inorganic, organic, and arsine gas. Organic arsenic is less toxic than inorganic arsenic and arsine gas. |
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Term
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Definition
| Binds to and depletes lipoate, resulting in inhibition of the Krebs cycle and depletion of ATP. |
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Term
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Definition
| DMSA/succimer (what is used to tx lead poisoning in kids) |
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Term
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Definition
| Cannot destroy heavy metals, but you can convert them into less toxic substances. This is the formation of a metal ion complex in which the metal ion is associated w/a charged or uncharged electron donor. Uses same technique the body uses- give SH grps, anything they like to compensate their electron deficiency. Metals are forming complexes in which the ligands contribute their unshared electrons to maintain charge balance w/positive charged metal center. ex-EDTA, DMPS, DMSA, Dimercaprol, Penicillamine, Deferoxamine |
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Term
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Definition
| Common chelator. Used in lead poisoning in kids and adults (method of choice). Lead binds and displaces calcium in the complex. |
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Term
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Definition
| Chelator for acute As, Hg, and Pb (when used w/EDTA). Toxic, so now DMPS is used more frequently |
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Term
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Definition
| Used for Hg and Pb poisoning. Administered orally and fewer side effects than BAL. |
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Term
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Definition
| Removes Pb in kids and main tx for As |
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Term
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Definition
| Rheumatoid arthritis and copper poisoning. Interval therapy allows essential biological metals to be replaced |
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Term
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Definition
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Term
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Definition
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Term
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Definition
| Volume of blood that is cleared of drug per unit time. Kel/C=.7Vd/t1/2 |
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Term
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Definition
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Term
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Definition
| ECF (1/3 TWB)Vd if it distributes like free water (escapes vasculature but is not take up by cells) |
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Term
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Definition
| Plasma (1/12 TBW). If it doesn't get out of vasculature at all, but doesn't enter cells in the blood |
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Term
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Definition
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Term
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Definition
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Term
| Lower pH causes release of what from Hb? |
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Definition
| Oxygen or CO2, whichever is bound |
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Term
| Pt presents w/cyanosis, chocolate colored blood and black tongue w/hemolytic anemia. Diagnosis? |
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Definition
| Methemoglobinemia. Further denaturation of globin chains forms precipitates that selectively stain in RBCs and are known as Heinz bodies. May be caused by exposure to oxidant drugs, chemicals, or inherited (HbM more susceptible to oxidation), genetic deficiencies in the metHb-reductase enzyme compromise the RBCs ability to reduce metHb |
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Term
| Pt presents w/dizziness, tachypnea, dyspnea, garlic odor to breath, cyanosis, pulmonary edema, sweating, anxiety, acidic and burning taste, hyperthermia, and frothing at the mouth and vomiting |
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Definition
| CN poisoning. Either through inhalation, ingestion, or through absorption. |
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Term
| Primary antioxidant defense mechanism |
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Definition
| Peroxidase activity. GSH is the major reducing agent in the RBC and it is essential for peroxidase activity. The SH grp of GSH provides the antioxidant reducing potential of GSH |
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Term
| Pt presents w/hemolytic, normocytic, normochromic anemia with increased BPG |
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Definition
| PK deficiency. AR. Decreased production of ATP compromises repair processes, leading to a hemolytic anemia. BPG and other pathway intermediates build up. Tx- transfusion. |
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Term
| Pt presents w/vomiting, diarrhea, and bleeding, followed by a quiet phase. Later, he seizes, coagulates, undergoes vascular collapse, and slips into a coma |
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Definition
| Acute iron toxicity. Most likely ingestion of iron pills (chronic iron overload=transfusion, defective erythropoiesis, and hereditary hemachromatosis) |
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Term
| Middle age pt presents w/liver, heart, pancreas, and skin problems. History of this in his family |
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Definition
| Hereditary hemochromatosis. AR disorder effecting transferri receptor, ferroportin, and receptor accessory proteins. Hemachromatosis is a disorder that interferes w/the body's ability to break down iron, and results in too much iron being absorbed from the GI tract. Tx- phlebotomy to remove iron |
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Term
| What happens to the Hb binding curve in anemia? |
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Definition
| Shifts to the right thanks to increased BPG in order to compensate |
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Term
|
Definition
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Term
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Definition
| Binds free Hb. Decreased in hemolytic anemia bc its all bound up |
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Term
| Young child with mild-moderate normocytic anemia and splenomegaly and parent who had a similar problem |
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Definition
| HS. Mild to moderte normocytic anemia w/high RDW. Reticulocytosis, spherocytes in peripheral blood smear. Hypercellularity w/compensatory erythroid hyperplasia. Will have chronic lifelong mild anemia that is alleviated by splenectomy. |
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Term
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Definition
|
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Term
| Malaria, babesia, clostridium |
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Definition
| Intracellular RBC parasites. Cause hemolysis |
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Term
| 1ml of blood cells contains x mgs of iron |
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Definition
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Term
| A man w/a hematocrit of 50% is bleeding 20ml/day. His diet includes 50mg/day of iron. How much is he losing and absorbin? |
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Definition
| Loses .5X20 (50% of his blood volume is RBC volume)=10ml blood cells=10mg Fe/day. He's absorbine .1X50=5mg Fe/day. 10-5=5mg Fe lost. |
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Term
| TIBC saturation in iron deficiency anemia |
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Definition
| Low. Serum iron/TIBC X 100. Lots of transferrin bc low ferritin stimulates increased transferrin. |
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Term
| When do you see free protoporphyrin in cells? |
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Definition
| Iron deficiency anemia and Pb poisoning |
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Term
|
Definition
| High. Epo also works on megakaryocytes |
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Term
| Macrocytic anemia with high RDW |
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Definition
| Immune mediated hemolysis and megaloblastic anemia. |
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Term
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Definition
| Low relative to the degree of anemia. TNF alpha, Il-C, and interferon gamma are cytokines that decrease epo and increase hepcidin |
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Term
| 4 times you're going to see sideroblastic anemia |
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Definition
| This is a microcytic anemia, and the sideroblasts are caused by an iron build up in mitochondria as heme can't get out of mitochondria. Mitochondria around nucleus in the bone marrow. 1. Pb poisoning 2. ALAS/B6 deficiency 3. Isoniozide for TB (decreases B6) 4. Alcohol (messes w/mitochondria) |
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Term
|
Definition
| All except heterozygous thal and SS have high RDWs |
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Term
| RDWs in production anemia |
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Definition
| Only elevated in megaloblastic (macrocytic) and IDA (microcytic) |
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Term
| Normocytic w/normal RDW (4) |
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Definition
| Some anemia of chronic disease, acute blood loss, heterozygous SS, anemia of chronic renal failure |
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Term
| Microcytic with High RDW (3) |
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Definition
| Iron deficiency, homozygous thal, microangiopathic hemolytic |
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Term
|
Definition
| Heterozygous thal, some anemia of chronic disease (becomes microcytic when long standing) |
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Term
| Bleeding pt with normo-macrocytic anemia with normal RDW. |
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Definition
| Aplastic anemia. Bleeding is clue- other anemias that are macrocytic w/normal RDW are myelodysplasia and some liver disease |
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Term
| Macrocytic w/normal RDW (3) |
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Definition
| Aplastic anemia, myelodysplasia, some liver disease. All production problems. |
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Term
| Pt presents at a couple months of age w/fairly severe microcytic anemia w/high RDW, splenomegaly and bony abnormalities. No hyperbilirubinemia |
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Definition
| Homozygous beta thal. May be irritable, failure to thrive, scleral icterus. Hepatosplenomegaly is from extramedullary erythropoiesis |
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Term
| 20yr old pt presents with mild microcytic anemia w/normal RDW ane increased retics and RBC |
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Definition
| Heterozygous thal. Only other anemia that is microcytic w/normal RDW is anemia of chronic disease, but this would have low retics and erythroid hypoplasia. |
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Term
| Bone marrow and retics in thal |
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Definition
| Increased reticulocytes and erythroid hyperplasia. Microcytic- normal RDW in heterozygotes, high RDW in homozygotes |
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Term
| Electrophoresis in alpha thal |
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Definition
| HbH will show up in 3 deletion. 2 and 1 deletion will not have any HbH |
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Term
| Infant presents with moderate microcytic anemia with a high RDW. Hyperbilirubinemia |
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Definition
| Three deletion alpha thal "HbH" disease. Can be contrasted to homozygous beta thal (which also presents in infancy) by the hyperbilirubinemia. Not life shortening and less profound than homozygous beta thal. Will see HbH, falls in HbA, HbA2, and HbF. Will have schistocytes on peripheral smear |
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Term
| Normocytic w/high RDW (2/3) |
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Definition
| Homozygous SS, HS, and possibly G6PD |
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Term
| 45 year old male of Italian ancestry who has CBC performed prior to an inguinal hernia repair. High RBC, microcytic anemia w/high RDW |
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Definition
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Term
| 73yr old man admitted for Gram negative sepsis. Microcytic anemia with high RDW |
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Definition
| Microangiopathic hemolytic anemia. Sepsis lead to DIC. |
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Term
| 44yr old female with macrocytic anemia with high RDW and jaundice and high reticulocytes |
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Definition
| Autoimmune hemolysis. Only other macrocytic w/high RDW anemia is megaloblastic anemia, but this will have low retics |
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Term
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Definition
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Term
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Definition
| These are structurally homologous cofactors and are integral membrane proteins expressed in active form. TF is expressed on fibroblasts and only exposed when vessel is damaged. Thrombomodulin is expressed on intact vascular endothelium |
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Term
| Thrombin as an antifibrinolytic |
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Definition
| Alpha thrombin becomes both an anticoagulant and an antifibrinolytic after binding thrombomodulin on the surface of vascular endothelial cells. TM-thrombin complex can bind to TAFIA and inhibits plasminogen activation catalyzed by tPA |
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Term
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Definition
| A study which involves identifying pts who have the outcome of interest (cases) and patients without the same outcome (controls) and then looking back to see if they had the exposure. Observational and retrospective. Measure by odds ratio. Good bc it is inexpensive and useful for outcomes that are rare or can develop over a long period of time |
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Term
| Cons to case-control study |
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Definition
| Often difficult to choose an appropriate control group, recall bias can complicate data, results can indicate an association but not risk or incidence rates. |
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Term
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Definition
| A study that identifies two groups of pts, one w/the exposure and one w/o, and follows these cohorts forward for the outcome of interest. Observational and prospective. Meausre with RR and incidence rates and CIs can be calculated. Pro- the temporal sequence btw exposure and outcome is usually clear, and the study avoids recall bias |
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Term
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Definition
| Can be prohibitively expensive when outcomes are rare or develop over a long period of time. Selection bias can result from participants dropping out of a study |
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Term
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Definition
| Involves observation of a defined population at a single point in time or time interval. The exposure and outcome are determined simultaneously. Pros- looks at prevalence, and may not be as time consuming |
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Term
| Cons to cross-sectional study |
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Definition
| Temporal relationships btw outcome and exposure may be unclear as both are examined at the same time |
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Term
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Definition
| Exposure assigned by the investigator. Participants are randomly allocated to an experimental grp or a control grp and followed over time for the variables/outcomes of interest. Pros- avoids selection bias. By controlling biases, RCT can pick up small differences, whereas in observational studies, small differences may be attributible to bias |
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Term
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Definition
| Proportion of new cases of the target disorder in the population at risk during a specified interval of time. #new cases of disease per unit time/total# of ppl at risk |
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Term
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Definition
| The proportion of ppl w/the target disorder in the pop at risk at a specific time. =# of cases present in the pop at a certain time/#persons in the pop at that specific time=incidence Xaverage duration of illness |
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Term
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Definition
| Measures strength of association btw outcome and exposure. Incidence in exposed pop/incidence in unexposed. Used for cohort and experimental studies |
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Term
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Definition
| ad/bc. Used for case controlled, retrospective studies |
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Term
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Definition
| TP/(TP+FN). Proportion of ppl with the target disorder who have a positive result. The ability to detect ppl who do have the disease. SNNOUT- SeNsitive test with a Negative result rules OUT the diagnosis (low false-negative is what you're going for) |
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Term
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Definition
| TN/(FP+TN). Proportion of ppl without the target disorder who have a negative test. Ability to detect ppl who do not have the disorder. SpPin- Specific test with a positive result rules in the diagnosis (low false-positive rate) |
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Term
| Do you give platelets in ITP? |
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Definition
| No- they will just get cleared. Instead, if needed, give glucocorticoids, IVIG, anti-RH IG, Rituximab, and consider splenectomy |
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Term
| Phenobarbitol, Polycyclic aromatic hydrocarbons (PAH) |
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Definition
| In addition to St. John's Wart, these are inducers of the P450 |
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Term
| Ketoconazole, omeprazole, cimetidine, probenecid, macrolides/erythromycin |
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Definition
| Inhibitors of the P450 system. This is in addition to grapefruit juice |
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Term
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Definition
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Term
| Hemorrhagic disease of the newborn |
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Definition
| Prevent by giving Vit K. Infants are prone to be Vit K deficient. A three day old girl born at home develops bloody stools and becomes lethargic |
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Term
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Definition
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Term
| Low PC, microcytic anemia w/high RDW.Renal fxn abnormalities, neurological symptoms, weakness, abdominal symptoms, low grade fever |
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Definition
| TTP. NO antibodies against RBCs, but may have antibodies against metalloprotease that cleaves vWF. Schistocytes |
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