Term
| What directs the differentiation/ maturation of cells from pluripotent stem cells? |
|
Definition
| Cytokines/ Interleukins/ Colony Stimulating Factors |
|
|
Term
| What is the cytokine that controls erythrocyte production? |
|
Definition
|
|
Term
| How does Erythropoietin Direct Erythrocyte Development? |
|
Definition
| The erythropoietin receptor on erythrocyte precursors has tyrosine kinase activity, and it activates a series of other intracellular kinases that increase the proliferation, growth, and development of erythrocyte precursors. |
|
|
Term
| What is the usual stimulus for the release of erythropoietin? |
|
Definition
| Tissue Hypoxia (Caused by low blood volume, anemia, low hemoglobin, poor blood flow, and/ or pulmonary disease) |
|
|
Term
| What is HIF-1? How does it work? |
|
Definition
| HIF-1 is the link between erythropoietin concentration and tissue hypoxia. Hypoxia-inducible factor (HIF) is made of alpha and beta subunits. HIF-1alpha is subject to degradation by proline hydroxylase in the presence of oxygen and iron, whereas HIF-1beta is constitutively expressed. When hypoxia is present, HIF-1alpha increases in concentration, combines with the HIF-1beta subunit to form the dimer, which then activates HIF-1 dependent target genes, such as those for erythropoietin, VEGF and GLUT-1 glucose transporter. HIF-1 is a master regulator of overall oxygen homeostasis through its effects on erythropoiesis, energy metabolism, and vascular remodeling. |
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|
Term
| What are the major events in erythrocyte maturation? |
|
Definition
| The accumulation of hemoglobin in the cytoplasm of the cell, the development of a pyknotic nucleus that is eventually extruded, and a reduction in cell size with each division. |
|
|
Term
| What is the average lifespan of a RBC? |
|
Definition
|
|
Term
|
Definition
| Iron that is absorbed from the GI tract, released from intracellular stores, or freed as the result of erythrocyte and hemoglobin turnover, circulates in the plasma in the form of transferrin. Transferrin with two iron atoms bound has a very high affinity for surface receptors on the marrow erythroid cells. Upon binding to these receptors, the transferrin-receptor complex is internalized, the iron removed, and most of the transferrin is returned to the circulation. |
|
|
Term
| What is the Total Iron Binding Capacity (TIBC)? |
|
Definition
| The total number of iron binding sites, occupied or not. |
|
|
Term
|
Definition
| Inside the cell, iron is bound to the intracellular storage protein apoferritin, forming ferritin. |
|
|
Term
| What causes most megaloblastic anemias? |
|
Definition
| A deficiency in folic acid and/or cobalamin (vit. B12) |
|
|
Term
|
Definition
| During gastric digestion, cobalamin in food is released and forms a complex with gastric R binder. On entering the duodenum, the cobalamin-R binder complex is digested, releasing the cobalamin, which then binds to intrinsic factor (IF). IF binds to the B12, protecting it from digestion, and eventually binds to receptors on the brush borders of mucosal cells lining the ileum, facilitating the absorption of B12 and its transport into the bloodstream. |
|
|
Term
|
Definition
| In the bone marrow and liver. |
|
|
Term
|
Definition
| Disorders of heme synthesis. 7 different kinds of porphyrias have been distinguished, representing discrete deficiencies of each of the 7 enzymes beyond the first and rate-limiting step of the synthetic pathway of heme. Porphyrias take 2 major forms: thalassemias and hemoglobinopathies |
|
|
Term
| Symptoms of abnormal heme synthesis |
|
Definition
| Photosensitivity, strong abdominal pain, port wine-colored urine, weakness or paralysis in the arms and legs, and behavioral changes (anxiety, irritability and confusion) |
|
|
Term
| Definition of Hemoglobinopathy |
|
Definition
| A disorder in which the hemoglobin chains produced are abnormal |
|
|
Term
| Definition of Thalassemia |
|
Definition
| A disorder in which the hemoglobin chains produced are normal in structure, but are decreased in amount or even absent. |
|
|
Term
| Which Inherited Red Cell Disorders are Protective Against Malaria? |
|
Definition
| Hemoglobin S (seen in Sickle Cell), Thalassemias, and G-6-PD deficiency are inherited red cell disorders associated wtih a reduction in the morbidity and mortality associated with infection by the malaria parasite. |
|
|
Term
| What is the only enzyme in the body that produces CO? |
|
Definition
|
|
Term
| Is conjugated bilirubin soluble or insoluble? |
|
Definition
|
|
Term
| Is unconjugated bilirubin soluble or insoluble? |
|
Definition
|
|
Term
| What is the form that most bilirubin is in? |
|
Definition
|
|
Term
| If levels of Unconjugated Bilirubin are High, Where is the problem? |
|
Definition
| Liver problem or there is increased hemolysis |
|
|
Term
| If Levels of Conjugated Bilirubin are High, Where is the Problem? |
|
Definition
|
|
Term
| What Enzyme Converts Unconjugated Bilirubin to Conjugated Bilirubin? |
|
Definition
| Uridine diphosphate glucuronyltransferase |
|
|
Term
|
Definition
| Made in the tissues; Insoluble in plasma; Bound to albumin; Elevated in hepatic disease; Elevated with hemolysis |
|
|
Term
|
Definition
| Made in the Liver; Soluble in plasma; Elevated in biliary disease |
|
|
Term
| What Happens to RBCs Without ATP? |
|
Definition
| They can't maintain appropriate concentrations of cations inside and outside of the cell and they expand and lyse |
|
|
Term
| What is the glucose transporter in RBCs? |
|
Definition
| GLUT 1, which is not insulin sensitive |
|
|
Term
| What enzyme catalyzes the phosphorylation of glucose to G-6-P in the RBC? |
|
Definition
|
|
Term
| Is glycolysis in the RBC aerobic or anaerobic? |
|
Definition
|
|
Term
| What reaction must occur in the RBC to maintain glycolysis? |
|
Definition
|
|
Term
|
Definition
| A tripeptide consisting of glutamic acid, cysteine (-SH group) and glycine; It protects cells from oxidating damage; Requires NADPH for conversion from oxidized to reduced form |
|
|
Term
|
Definition
| It comes from the Pentose Phosphate Pathway, G-6-P dehydrogenase produces it |
|
|
Term
| What is a compound that is common to both the Pentose Phosphate Pathway and Glycolysis? |
|
Definition
|
|
Term
| The risk of a false negative result for an assay of G-6-PD Activity can be decreased if the blood sample is analyzed... |
|
Definition
| After differential centrifugation to isolate the oldest cells |
|
|
Term
|
Definition
| It is a cofactor for methionine synthase, which helps to trap folic acid within the cell (if you can't trap folic acid withing the cell, then you can't complete DNA synthesis); B12 also is required to complete the conversion of homocysteine to methionine, which is used to myelinate nerves (which is the cause of the neuro s/s seen in B12 deficiency). |
|
|
Term
| Methylmalonate in the Urine |
|
Definition
| Suggests a B12 deficiency; If there is no B12, L-methylmalonyl CoA can't be converted into Succinyl CoA, so it builds up and then (after a few intermediate steps) is excreted in the urine as methylmalonate, which can be measured |
|
|
Term
| Role of HCl in B12 Absorption/ Intake. |
|
Definition
| HCl breaks the bond between B12 and R-binder, so that B12 is then free to bind with intrinsic factor. |
|
|
Term
| Role of HCl in Iron Intake |
|
Definition
| Iron in food is in the Ferric (Fe3+) form and it needs to be in the Ferrous (Fe2+) form in order to be absorbed - HCl plays a role in this conversion |
|
|
Term
| How is the Iron Balance in Humans Controlled? |
|
Definition
| By regulation of absorption (since you don't really excrete iron) |
|
|
Term
|
Definition
| A severe skin reaction upon sun exposure seen in patients with porphyria |
|
|
Term
| What type of anemia is caused by defects in the hexose monophosphate sunt/ pentose phosphate pathway? |
|
Definition
|
|
Term
| Excessive heme degradation will result in... |
|
Definition
|
|
Term
|
Definition
| Production of formed blood elements; Normally occurs in bone marrow |
|
|
Term
| Cellularity of Bone Marrow |
|
Definition
| Ratio of Cells to Fat; Rough estimate of what the ratio should be = 100-Age (ex: patient is 90, 100-90 = 10, so they should have 10 cells: 90 fat); Helps you determine if the marrow is hypercellular (more cells than expected) or hypocellular (fewer cells than expected) |
|
|
Term
|
Definition
| The ratio of granulocytes to red cells; In a normal adult, the ratio is 3:1 |
|
|
Term
| What are the 3 Ways that Anemias are Classified/ the 3 Things Anemia May be Secondary to? |
|
Definition
| 1) Blood Loss (Acute v. Chronic); 2)Increased Destruction of RBCs (hemolysis) - intrinsic v. extrinsic RBC abnormalities; 3) Impaired Red Cell Production - defective DNA synthesis or defective hemoglobin synthesis |
|
|
Term
| Clinical Features (S/S) of Anemia |
|
Definition
| Pallor, Weakness, Dyspnea on exertion, Myocardial hypoxia, CNS hypoxia |
|
|
Term
| What is the most common nutritional deficiency? |
|
Definition
|
|
Term
| In which part of the GI tract is Iron absorbed? |
|
Definition
|
|
Term
| Etiology of Iron Deficiency |
|
Definition
| Dietary Lack (elderly, infants, children, rare in industrialized nations); Impaired Absorption (sprue, chronic diarrhea); Increased Requirements (growing infants, pregnant women); Chronic Blood Loss (external hemorrhage, GI/GU tract) |
|
|
Term
| Morphology of Iron Deficiency Anemia |
|
Definition
| Peripheral Blood Smear - hypochromia, microcytosis; Bone Marrow - decreased to absent stores of iron |
|
|
Term
|
Definition
| A "rule" to help determine if a cell is normo-, hypo- or hyperchromic; In a normochromic RBC, the outer 1/3 should be red, the middle 1/3 should be pale (zone of pallor), and the other outer 1/3 should be red |
|
|
Term
| Laboratory Diagnosis of Iron Deficiency Anemia |
|
Definition
| Decreased serum iron, Decreased serum ferritin (an iron storage protein); Increased total iron binding capacity; Decreased transferrin saturation (a transport protein); Decreased MCV; Absent storage iron in the bone marrow |
|
|
Term
| What is the Cause of Megaloblastic Anemia? |
|
Definition
| Impaired DNA synthesis (results in giant red cells and giant myeloid precursors); Principle causes of impaired DNA synthesis - vitamin B12 deficiency and/ or folate deficiency (because B12 and folate are precursors/ coenzymes necessary for DNA synthesis) |
|
|
Term
| Nuclear: Cytoplasmic Asynchrony |
|
Definition
| Seen in megaloblastic anemias; The nucleus is not maturing (because DNA synthesis is impaired) and the cytoplasm is |
|
|
Term
| In Which part of the GI tract is B12 absorbed? |
|
Definition
|
|
Term
| What is the major source of B12? |
|
Definition
|
|
Term
| What are the biochemical functions of B12? |
|
Definition
| DNA synthesis, Maintenance of Myelin |
|
|
Term
| Etiologies of B12 Deficiency |
|
Definition
| Dietary deficiency (strict vegetarians); Impaired absorption (intrinsic factor deficiency - pernicious anemia, gastrectomy - Malabsorption); Competitive uptage (ex: parasites); Increased requirement (pregnancy) |
|
|
Term
| What is the most common cause of B12 deficiency? |
|
Definition
|
|
Term
|
Definition
| Autoimmune destruction of the gastric mucosa, which leads to a loss of parietal cells. Since the parietal cells are what make intrinsic factor, the levels of intrinsic factor are markedly decreased, which, in turn, means that B12 cannot be absorbed in the terminal ileum leading to a deficiency in B12. |
|
|
Term
| Autoantibodies involved in Pernicious Anemia |
|
Definition
Anti-intrinsic Factor: IgG, 75% of patients with pernicious anemia have this, it's the more specific of the two antibodies (i.e. if you detect it, the patient more than likely has pernicious anemia);
Anti-Parietal Cell Antibody: IgG, 85-90% of patients have this, It's the more sensitive of the two tests (i.e. if you DON'T detect it, the patient likely doesn't have pernicious anemia, however if you DO detect it they may OR may not have pernicious anemia) |
|
|
Term
| Peripheral Blood Smear Morphology of B12 Deficiency |
|
Definition
| Macro-ovalocytes, Hypersegmented neutrophils |
|
|
Term
| Morphology of Bone Marrow in B12 Deficiency |
|
Definition
| Hypercellular, Megaloblasts, Giant Bands |
|
|
Term
| CNS involvement with B12 Deficiency |
|
Definition
| Myelin Degeneration, "subacute combined degeneration" |
|
|
Term
| Diagnosis of B12 Deficiency |
|
Definition
| Macro-ovalocytes (macrocytosis); Hypersegmented neutrophils; Neurologic manifestations, Serum autoantibodies (with Pernicious anemia); Eleveated serum methylmalonic acid; Low serum B12; Schilling Test |
|
|
Term
|
Definition
| Patients are given an B12 injection to saturate binding sites within the body. An oral, radiolabeled dose of B12 is given and a 24 hour urine is collected. In pernicious anemia, radiolabeled B12 is not present in the urine, since the oral dose is not absorbed (part I of the test). In part II, intrinsic factor is given with oral B12 - NOW, radiolabeled B12 is detected in the urine of PA patients becuase the administered IF forms the B12-IF complex required for absorption in the terminal ileum (and the binding sites were all occupied, so none of the radiolabled B12 was bound up there) |
|
|
Term
| What is the richest source of Folate? |
|
Definition
|
|
Term
| Etiology of Folate Deficiency |
|
Definition
| Decreased intake (alcoholics, indigents); Increased requirements (pregnancy, infancy); Impaired utilization (folate antagonists) |
|
|
Term
| Morphology of Folate Deficiency |
|
Definition
| Peripheral Blood Smear - macro-ovalocytes, hypersegmented neutrophils; Bone marrow - megaloblasts (with "salami-like" chromatin), giant bands and metamyelocytes |
|
|
Term
|
Definition
| Associated with megaloblasts (as seen in megaloblastic - folate and B12 deficient - anemias); There is a really sharp separation of clear spaces (euchromatin, active DNA) and dark areas (heterochromatin, inactive DNA) |
|
|
Term
| Laboratory Diagnosis of Folate Deficiency Anemia |
|
Definition
| Decreased serum folate levels; Decreased RBC folate levels (more accurate than serum folate levels b/c serum levels are more diet-dependent); Elevated formiminoglutamic acid; Resolution of S/S following folate administration |
|
|
Term
| What is the probably most common cause of anemia in the hospital setting? |
|
Definition
| Anemia of Chronic Disease (AOCD) |
|
|
Term
| Anemia of Chronic Disease (AOCD) |
|
Definition
| Extremely common; Impaired RBC production; Defective Iron utilization |
|
|
Term
| Chronic Illnesses Associated with Anemia of Chronic Disease |
|
Definition
| Infection - typically long-standing and difficult to treat (osteomyelitis, lung abscesses, endocarditis, etc); Immune Disorders (RA, Chron's); Neoplasms (Hodgkin's ds, Carcinoma) |
|
|
Term
| Etiology of Anemia of Chronic Disease |
|
Definition
| Elevated cytokines (IL-1, TNF); Diversion of iron to the storage pool as a result of cytokine presence; Defective hemoglobin synthesis as a result of being unable to access the stored iron; Decreased RBC survival |
|
|
Term
| Morphology of Anemia of Chronic Disease |
|
Definition
Peripheral Blood Smear - normocytic/ normochromic or microcytic/hypochromic, Rouleaux formations;
Bone Marrow - increased iron storage, decreased erythroid iron |
|
|
Term
|
Definition
| Seen in Anemia of Chronic Disease; RBCs pile up on top of each other (like a stack of coins) because while they normally have negative charges which repel each other, the cytokines present in chronic disease states are positively charged and they neutralize the negative charge on the RBC and the RBCs no longer repel each other |
|
|
Term
| Laboratory Diagnosis of Anemia of Chronic Disease |
|
Definition
| Low serum iron; Decreased or Normal Total Iron Binding Capacity (this helps differentiate between AOCD and iron-deficient anemia becuase TIBC is increased in iron deficient anemia); Elevated serum ferritin (decreased in iron deficient anemia); Increased marrow storage iron |
|
|
Term
|
Definition
| Shortened RBC life span; Hg catabolic end products (eg bilirubin); Marrow erythroid hyperplasia (bone marrow is trying to compensate for the anemia) |
|
|
Term
|
Definition
Intravascular - normal RBCS, destruction within vasculature (mechanical trauma, exogenous toxins, complement fixation);
Extravascular/ Splenic - More common, RBCs are rendered foreign, destruction in spleen |
|
|
Term
| Manifestations of Intravascular Hemolysis |
|
Definition
| Jaundice, Gallstones, Hemoglobinemia, Hemoglobinuria, Decreased Haptoglobin |
|
|
Term
| Manifestations of Extravascular Hemolysis |
|
Definition
|
|
Term
| Cause of Jaundice in Hemolytic Anemias |
|
Definition
| Secondary to bilirubin deposition in the skin, sclera, etc. |
|
|
Term
| Cause of Gallstones in Hemolytic Anemia |
|
Definition
| Secondary to bilirubin precipitating out in the gallbladder |
|
|
Term
| Cause of Hemoglobinemia in Hemolytic Anemia |
|
Definition
| RBCs lyse and release their Hg into the serum, so there is an increase in free Hg in serum |
|
|
Term
| Cause of Hemoglobinuria in Hemolytic Anemia |
|
Definition
| The excess free Hg in the serum spills over into the urine |
|
|
Term
| Cause of the Decreased Haptoglobin in Hemolytic Anemia |
|
Definition
| Haptoglobin is a protein that binds free Hg (which is elevated in hemolytic anemia); Once it is bound to Hg, the is cleared by the liver - so with extra free Hg to be mopped up, extra haptoglobin will subsequently be cleared, decreasing its levels |
|
|
Term
|
Definition
| Autosomal Dominant; Spheroidal RBCs; A form of extravascular hemolysis (since there is splenic destruction of the spheroidal RBCs) |
|
|
Term
| Pathogenesis of Hereditary Spherocytosis |
|
Definition
Inherited Ankyrin deficiency which leads to reduced membrane stability and loss of fragments of the membrane. The RBCs then adopt a spheroidal shape, which is less deformable than the normal bi-concave disc and the abnormal RBCs are then removed by the spleen, resulting in anemia;
NOTE - Ankyrin is what Dr. Christman said is the protein involved, Dr. Thompson said it was Spectrin (which is what they used to think was the primary cause, but recent studies have found it to be ankyrin - so either one could be the correct answer on an exam question depending on who wrote the question) |
|
|
Term
| Morphology of Hereditary Spherocytosis |
|
Definition
| Peripheral Blood Smear - spherocytes; Bone Marrow - erythroid hyperplasia; Splenomegaly; Pigmented gallstones |
|
|
Term
| Clinical Course of Hereditary Spherocytosis |
|
Definition
| Mild to severe hemolytic anemia; The patient can develop hemolytic and/ or aplastic crises |
|
|
Term
|
Definition
| Seen in patients with Hereditary spherocytosis; Results in massive hemolysis; Usually secondary to an overactive spleen (becuase the spleen is a lymphoid organ, it reacts to infection and becomes hyperactive) |
|
|
Term
|
Definition
| Seen in Hereditary Spherocytosis and Sickle Cell Anemia; Results from a Parvovirus Infection; Parvovirus preferentially targets erythroid precursors in the bone marrow, so the bone marrow can't compensate for the anemia by being hypercellular like it usually would in patients with HS or SC, so the patient goes into crisis |
|
|
Term
| Diagnosis of Hereditary Spherocytosis |
|
Definition
| Family history (becuase it's autosomal dominant); Peripheral blood smear (presence of spherocytes); Osmotic fragility test (increased fragility, RBCs break down at lower than normal osmotic pressures) |
|
|
Term
| Treatment of Mild Hemolysis |
|
Definition
| Supportive; Make sure the patient doesn't go into crisis and treat them if they do |
|
|
Term
| Treatment of Severe Hemolysis |
|
Definition
|
|
Term
|
Definition
| Production of abnormal Hg; Point mutation in the Beta chain of Hg; Hemoglobin S (HgS) |
|
|
Term
|
Definition
A tetramer of 4 globin chains;
96% of Hg is HgA (2 alpha chains, 2 beta); 3% is HgA2 (2 alpha chains, 2 delta); 1% is HgF (fetal hemoglobin, 2 alpha chains, 2 gamma) |
|
|
Term
| Homozygous Gene Dosage in Sickle Cell Anemia |
|
Definition
| These patients have sickle cell disease; Inherit 2 copies of the mutation; HgS makes up 90-100% of total Hg; NO HgA |
|
|
Term
| Heterozygous Gene Dosage in Sickle Cell Anemia |
|
Definition
| These patients have sickle cell trait; Inherit 1 copy of mutation; HgS makes up 40-45% of total Hg |
|
|
Term
| Pathogenesis of Sickle Cell Anemia |
|
Definition
| HgS, upon deoxygenation, polymerizes with other HgS molecules in the same RBC, this causes distortion/ sickling of the RBC; Initially, this is reversible following re-oxygenation of the RBC, but after enough cycles it becomes irreversible |
|
|
Term
| Consequences of RBC Sickling |
|
Definition
| Chronic Hemolytic Anemia (jaundice, gallstones); Occlusion of Small Blood Vessels (Ischemia/ thrombosis) |
|
|
Term
| Determinants of Sickling Severity |
|
Definition
| Amount of HgS in the RBC (Homozygotes have more sickling than heterozygotes); Hg Concentration (sickling increases with dehydration); pH (Acidosis) |
|
|
Term
| Morphology of Sickle Cell Anemia |
|
Definition
| Peripheral Blood Smear - sickle cells; Bone Marrow - erythroid hyperplasia; Spleen - splenomegaly in kids, small fibrotic spleen in adults as a result of ischemia; Ischemic Damage; Gallstones |
|
|
Term
| Clinical Course of Sickle Cell Anemia |
|
Definition
| Homozygotes - long-term, chronic anemia; Heterozygotes - basically asymptomatic unless they get dehydrated; Patients can develop vaso-occlusive, aplastic, and sequestration crises |
|
|
Term
| Diagnosis of Sickle Cell Anemia |
|
Definition
| Family History; Peripheral Blood Smear (sickle cells - if you see sickle cells in the peripheral smear, the patient is likely homozygous); Laboratory - sickling studies (to test the peripheral blood of a heterozygote in whom you wouldn't otherwise see sickling in the peripheral blood smear), Hemoglobin electrophoresis (HgA, HgA2, HgF, and HgS cause peaks at different points and the area under the peak indicates relative amount of that Hg present) |
|
|
Term
|
Definition
| An enzyme in the hexose monophosphate shunt that reduces NADP to NADPH. NADPH subsequently provides the reducing power that converts oxidized glutathione to reduced glutathione, which in turn protects the RBC and its membrane from endogenous and exogenous oxidants. Deficiency in G6PD leads to hemolysis |
|
|
Term
|
Definition
| An abnormal genetic variant of G6PD that is found in 10% of American blacks; The enzyme is synthesized in normal amounts, but is unstable with a short half-life resulting in a marked deficiency in (and therefore hemolysis of) older red cells |
|
|
Term
|
Definition
| An abnormal genetic variant of G6PD that is found in Middle Eastern extraction; In this case the enzyme is very unstable and leads to hemolysis of both older AND younger RBCs |
|
|
Term
| Oxidant Injury Associated with G6PD Deficiency |
|
Definition
| Drug Induced: anti-malarials (primaquine, quinacrine), antibiotics (sulfonamides); Infections |
|
|
Term
| Diagnosis of G6PD Deficiency |
|
Definition
| Clinical history (episodic hemolysis); Peropheral Blood Smear - Heinz bodies, Bite cells; G6PD levels |
|
|
Term
|
Definition
| Seen in peripheral blood smears in patients with G6PD Deficiency; H2O2 accumulates in the cells of G6PD deficient patients and causes oxidative destruction of Hg. The denatured Hg then forms precipitates in the RBC (the Heinz bodies) which can be visualized in the peripheral smear following special staining |
|
|
Term
|
Definition
| Seen in patients with G6PD Deficiency; As RBCs with Heinz bodies pass through the spleen, the Heinz bodies are "plucked" out by macrophages, giving rise to RBCs that appear to have a bite of cytoplasm removed. the resultant loss of membrane induces spherocyte formation which predisposes to RBC destruction by the spleen |
|
|
Term
|
Definition
| Decreased synthesis of Hg chains; the Hg is structurally normal, there's just not enough of it |
|
|
Term
|
Definition
| Beta Thalassemia - deficient beta chain synthesis; Alpha Thalassemia - deficient alpha chain synthesis |
|
|
Term
| Hematologic Consequences of Thalassemia |
|
Definition
| Low Intracellular Hg (hypochromia, microcytosis); Relative Excess of the Normal Chain (ex: excess alpha chains in beta thalassemia) - insoluble complexes (eg the excess chains that come together precipitate out), ineffective hematopoiesis, hemolysis |
|
|
Term
| Disorders that Result in Hypochromic, Microcytic Cells |
|
Definition
| Iron Deficiency, Thalassemia, and Anemia of Chronic Disease |
|
|
Term
| Molecular Pathogenesis of Beta Thalassemia |
|
Definition
| The beta chain is encoded for by 2 genes (one on each chr 11)- beta thal results from a single base point mutation; The normal beta gene is "B"; Abnormal genes can either be "B0" (no synthesis of beta chain) or "B+" (low-level synthesis of beta chain) |
|
|
Term
| Clinical Syndromes of Beta Thalassemia |
|
Definition
| Based on severity of anemia - related to the genetic defect (B0 vs B+) and the gene dosage (homozygous vs heterozygous); Homozygous (B0/B0, B+/B+) - Thalassemia Major; Heterozygous (B/B0, B/ B+) - Thalassemia trait |
|
|
Term
|
Definition
| Associated with Beta Thalassemia and the Alpha Thalassemia Trait form of Alpha Thalassemia |
|
|
Term
| Morphology of Beta Thalassemia |
|
Definition
| Peripheral Blood Smear - hypochromia/ microcytosis, target cells; Bone Marrow - erythroid hyperplasia, increased storage iron; Splenomegaly; Hemosiderosis |
|
|
Term
| Diagnosis of Beta Thalassemia |
|
Definition
| Clinical/ Family History; Peripheral Blood Smear; Elevated Levels of HgA2 (compensation becuase HgA levels are decreased in Beta thal); Alpha:Beta chain ratios |
|
|
Term
| Molecular Pathogenesis of Alpha Thalassemia |
|
Definition
| Alpha chains are encoded for by 4 genes (2 genes on each Chr.16) - Alpha Thalassemia is due to the deletion of one or more alpha gene(s); Normal Genotype - Alpha, Alpha/ Alpha, Alpha |
|
|
Term
| Clinical Syndromes Assoicated with Alpha Thalassemia |
|
Definition
| Based on severity of anemia - silent carrier state, alpha thalassemia trait, Hemoglobin H disease, hydrops fetalis |
|
|
Term
| Silent Carrier Form of Alpha Thalassemia |
|
Definition
| Deletion of a single Alpha globin gene (___, Alpha/ Alpha, Alpha); Asymptomatic, Difficult to diagnose in adulthood |
|
|
Term
| Alpha Thalassemia Trait Form of Alpha Thalassemia |
|
Definition
| Deletion of 2 Alpha globin genes - (___, Alpha/Alpha, Alpha) or (___, Alpha/ ___, Alpha); Mild Anemia; Peripheral blood smear shows hypochromia/ microcytosis and target cells |
|
|
Term
| Hemoglobin H Disease Form of Alpha Thalassemia |
|
Definition
| Deletion of 3 Alpha globin genes - (___, ___/ ___, Alpha); There's an excess of beta chains due to the underproduction of alpha chains, and these beta chains form tetramers, which are called Hemoglobin H; Moderately severe anemia; Dx - hemoglobin electrophoresis |
|
|
Term
| Hydrops Fetalis Form of Alpha Thalassemia |
|
Definition
| Deletion of all 4 alpha globin genes - (___,___/___,___); Occurs in fetuses - becuase Fetal Hg is made of 2 alpha and 2 gamma chains, there is an excess of gamma chains due to the underproduction of alpha chains, these gamma chains form tetramers known as Hemoglobin Barts which can bind O2, but has such a high affinity for it that it won't give it up to the tissues; Causes intrauterine fetal death |
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Term
|
Definition
| An excess of WBCs seen in inflammatory conditions; NEUTROPHILIA - acute inflammation, pyogenic infections, tissue necrosis; EOSINOPHILIA - allergies, parasites, drug reactions; MONOCYTOSIS - chronic infections; LYMPHOCYTOSIS - chronic and viral infections |
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Term
|
Definition
| Called leukemoid because it resembles leukemia, but it is benign; Severe leukocytosis with immature cells seen in peripheral blood |
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Term
| Morphology of Leukemoid Reaction |
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Definition
| Dhole Bodies (precipitated DNA); Toxic Granules (granules that are increased in size and number and can therefore be seen at a lower objective power than normal); Vacuolization (implies that the cell is phagocytizing something); These things distinguish leukemoid reaction from leukemia (which does not exhibit any of these characteristics) |
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Term
|
Definition
| A reduction in WBC number; Can have neutropenia, lymphocytopenia, eosinopenia, or monocytopenia; Neutropenia and Lymphocytopenia are the most common types |
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Term
|
Definition
| Seen in bacterial and fungal infections; Clinical Features - fever, malaise, chills, antimicrobial therapy, colony stimulating factors (drugs that stimulate the bone marrow to make neutrophils); ABSOLUTE NEUTROPENIA - <500 neutrophils, Absolute Neutrophil Count = wbc x % neutrophils; When the ANC is <500, the patient is at risk for life-threatening infections |
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Term
| Pathogenesis of Neutropenia |
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Definition
| Ineffective Neutrophil Production by the Bone Marrow (drugs - adults, infections - kids, aplastic anemia, marrow replacement); Accelerated Destruction - neutrophils are made at a normal rate/ amount, but they're destroyed peripherally (immune mediated, splenic sequestration); The 2 most common causes of Severe Neutropenia are drugs in adults and infections in kids |
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Term
| General Definition of Leukemia |
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Definition
| Malignant neoplasms of stem cells, which diffusely replace bone marrow; Tumor cells may be seen circulating in blood, but leukemias are primary disorders of bone marrow; 4 Types - Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Chronic Myeloid Leukemia, Chronic Lymphoid Leukemia |
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Term
|
Definition
| Leukemias are classified based on the predominate cell type and the clinical presentation; In ACUTE leukemias cells are immature and the clinical course is rapidly fatal if untreated; In CHRONIC leukemias cells are mature and the clinical course is more indolent |
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Term
| Characteristics of Immature Cells |
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Definition
| Big, Round nuclei (remember though, that mature lymphocytes also have round nuclei), Nucleoli, Diffuse/ uniform chromatin |
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Term
| Characteristics of Mature Cells |
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Definition
| Lobulated or small nuclei, Clumped chromatin, NO nucleoli |
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Term
|
Definition
| Clonal expansion of a stem cell, Failure of maturation (which is why the cells are immature); Clinical features include - abrupt onset, symptoms due to depressed marrow (anemia, infection, "bleeding out" due to thrombocytopenia), Lymphadenopathy, Hepatosplenomegaly, CNS infiltration - NOTE: when you have tissue infiltration, it's usually Acute Lymphoid Leukemia, rather than Acute Myeloid Leukemia |
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Term
| Laboratory Findings in Acute Leukemia |
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Definition
| Leukopenia or Leukocytosis; Anemia; Thrombocytopenia; Circulating blasts (Myeloblasts in AML, Lymphoblasts in ALL) |
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Term
| Since Myeloblasts and Lymphoblasts appear so microscopically similar, how do you differentiate the two when diagnosing AML and ALL? |
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Definition
| Look at Terminal deoxynucleotidyl transferase (Tdt) and myeloperoxidase levels; Myeloblasts will be myeloperoxidase positive and TdT negative, while lymphoblasts will be myeloperoxidase negative and TdT positive |
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Term
| Acute Lymphoid Leukemia (ALL) |
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Definition
| A disease of children - peak incidence of 4 years; Immunologic Types (Precursor B-cell and Precursor T-cell) distinguished via flow cytometry based on what CDs are present |
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Term
| Immunologic Classification/ Differentiation of Acute Lymphoid Leukemia Subtypes |
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Definition
| Based on antigen expression of tumor cells as detected by flow cytometry; Precursor B-Cell ALL - CD19, CD20, CD22 positive; Precursor T-Cell ALL - CD2, CD3, CD4 or CD7, CD8 positive; CHEESY PNEUMONIC: B-CELL has BIG number CDs, T-CELL has TINY number CDs |
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Term
|
Definition
| Most childhood ALL is B-cell type; Childhood ALL has an excellent prognosis; Adult ALL has a poor prognosis |
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Term
| Numeric ALL Karyotypic Abnormalities |
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Definition
| Abnormal number of chromosomes - Hyperdiploid (>50 chromosomes in tumor cells) = favorable prognosis; Pseudodiploid (46 chromosomes in tumor cells) cells may have structural abnormalities instead; Pseudodiploid confers an unfavorable prognosis |
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Term
| Structural ALL Karyotypic Abnormalities |
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Definition
Translocations with a BAD prognosis: t(4;11), t(1;19), t(9;22), t(8;14); Translocaitons with a GOOD prognosis: t(12;21);
NOTE: t(4;11) was in his handout, but not the powerpoint, and t(8;14) was in his powerpoint but not his handout |
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Term
| Prognosis for Childhood ALL |
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Definition
| Remission induced in 90% of childre with 2/3 of those effectively cured; Favorable Prognositc Factors - 2-10 years of age, Precursor B-cell type, hyperdiploidy, t(12;21) translocation; Unfavorable Prognostic Factors - translocations other than t(12;21), T-cell type, <1 year of age and adults; Tx may require allogenic marrow transplantation |
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Term
| Acute Myeloid Leukemia (AML) |
|
Definition
| Disease of adults between 15 and 39 years (this is the peak incidence, but AML can occur at any age); Heterogeneous cell types involved because of myeloid diversity (granulocytes, monocytes, erythrocytes, megakaryocytes) |
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Term
|
Definition
AML with Recurrent Cytogenic Abnormaliies - AML with t(8;21), AML with t(15;17), AML with inversion (16); AML with t(11q23); AML not otherwise specified (NOS) - categoriezed based on degree of differentiation and cell type affected;
NOTE: t(8;21), t(15;17) and inv (16) have a good prognosis, whereas t(11q23) has a bad prognosis |
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Term
|
Definition
| Morphology - myeloblast (immature cell, delicate chromatin, 3-5 nucleoli, AUER RODS); Defining Characteristics - Blasts comprise at least 20% of nucleated marrow elements, with or without peripheral blood involvement |
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Term
|
Definition
| Pathognomonic for AML - if they are present it's AML, if they're not it doesn't necessarily mean it's not AML; They are needle-like, red-staining inclusions in the cytoplasm of myeloblasts |
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Term
| Immunologic Characteristics of AML |
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Definition
| Myeloblasts have CD13, 15 and 33 |
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Term
| Promyelocytic Leukemia (M3) |
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Definition
| A form of AML in which abnormal promyelocytes dominate; t(15;17) is associated with a favorable prognosis; DIC often develops in these patients (as the result of degranulation of the promyelocytes); Morphology shows cells with hypergranular cytoplasm and multiple Auer rods |
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Term
|
Definition
| AML is dfficult to treat; There is a 60% remission rate with conventional chemotherapy, but only a 15-30% cure rate (i.e. disease free for 5 years) in that 60%; Tx may involve allogenic marrow transplantation |
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Term
| Myelodysplastic Syndromes (MDS) |
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Definition
| Clonal stem cell disorders, Maturational defects resulting in ineffective hematopoiesis, Increased risk of AML; Morphology - dysplasia of myeloid cells (abnormal nuclear lobulation, granule abnormalities, megaloblastoid features) |
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Term
| Ineffective Hematopoiesis |
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Definition
| The marrow is producing abnormal cells, which are destroyed in the marrow before reaching the peripheral blood; Becuase of this, the bone marrow is hypercellular with a concomitant peripheral blood pancytopenia |
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Term
|
Definition
| Based on specific morphologic features; WHO Scheme - Refractory anemia (RA), RA with Ring-Sideroblasts (RARS), RA with Excess Blasts Type I (RAEB- I), RA with Excess Blasts Type II (RAEB- II), RA with Multilineage dysplasia; RA and RARS are considered "low-grade" with only a small percentage progressing to AML, the rest are considered "high grade" |
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Term
| Refractory Anemia with Excess Blasts Type I (RAEB-I) vs. Refractory Anemia with Excess Blasts Type II (RAEB-II) |
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Definition
| RAEB-I has 5-10% Blasts, whereas RAEB-II has 10-19% blasts (essentially, this is the immediate precursor to AML which by definition has at least 20% blasts) |
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Term
| Clinical Presentation of MDS |
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Definition
| Affects older individuals (60-70yrs), Pancytopenia, Hypercellular Marrow, Chromosomal abnormalities, 10-14% of patients progress to frank AML |
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Term
|
Definition
| Hypercellular marrow, Dysplastic myeloid features |
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|
Term
| What are the Myeloproliferative Disorders? |
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Definition
| Chronic Myelogenous Leukemia (CML), Polycythemia Vera (P.vera), Myeloid Metaplasia with Myelofibrosis, Essential Thrombocythemia (ET) |
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Term
|
Definition
| The most common myeloproliferative disorder; Disease of adulthood (25-60 yrs old) with a peak incidence in the 4th and 5th decades |
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Term
|
Definition
| Neoplastic transformation of myeloid stem cell; Myeloid linages affected - Granulocytes (especially), erythrocytes, megakaryocytes |
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Term
|
Definition
Cytogenetics - translocation t(9;22) in 90% of cases, Philadelphia Chromosome (this is what the resultant chr 22 is known as);
Molecular Biology - BCR-ABL fusion gene (results from the t(9;22) translocation, and is seen in ~100% of CML cases) |
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Term
|
Definition
| Peripheral Blood - Marked leukocytosis (neutrophils, myelocytes, basophils); Bone Marrow - Marked hypercellularity, Increased myeloid:erythroid ratio (because of neutrophilia), Megakaryocyte clustering |
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Term
|
Definition
| Insidious onset, left upper quadrant dragging (due to splenomegaly), median survival of 3 years; Accelerated Phase - gradual treatment failure, transformation to acute leukemia (blast crisis), Increasing WBC count, anemia; Blast Crisis - transformation with at least 20% blasts (definition of AML) |
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Term
|
Definition
| Conventional chemotherapy - induces remissions, doesn't change survival; Marrow transplantation is the only definitive treatment and is the preferred treatment in young patients with stable disease (i.e. not in blast crisis); In a blast crisis, all forms of treatment are ineffective |
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Term
|
Definition
| There are 3 Types: Primary Absolute Polycythemia (P.vera), Secondary Absolute Polycythemia (due to renal masses), and Relative Polycythemia |
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Term
|
Definition
| Proliferation of erythroid, granulocytic and megakaryocytic elements; Absolute increase in RBC mass (becuase the dominant cell line affected are the erythroid precursors); Decreased erythropoietin (because there are so many RBCs present, EPO production isn't triggered); Jak-2 mutation (not specific for P.vera, but it is detected in 90-95% of p.vera cases) |
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Term
| Morphology of Polycythemia Vera |
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Definition
| Hypercellular marrow, erythroid hyperplasia, Decreased M:E ration (becuase while granulocytes and megakaryocytes are increased, erythrocytes are increased more) |
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Term
| Clinical Features of P. Vera |
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Definition
| Disease of late middle age; Congestion of tissues and organs (because of increased blood volume); Increased blood viscosity leading to vascular stasis, thrombosis and infarction; Pruritis (due to excess release of histamine from basophils); Gout (results from hyperuricemia from increased cell turnover); Elevated Hg and hematocrit |
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Term
|
Definition
| Therapeutic phlebotomies; Myelosuppresive treatment (Chlorambucil, P32) |
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|
Term
| Natural History of P.vera |
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Definition
| Median survival of 10 years; Spent phase (resembles myeloid metaplasia with myelofibrosis); Rare progression to AML |
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Term
| Myeloid Metaplasia with Myelofibrosis |
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Definition
| Neoplastic myeloid stem cell proliferation - occurs in the spleen (metaplasia, AKA extramedullary hematopoiesis), fibrotic marrow (myelofibrosis); Myelofibrosis is secondary to release of growth factors from neoplastic megakaryocytes (platelet derived growth factor and transforming growth factor beta) |
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Term
| Morphology of Myeloid Metaplasia with Myelofibrosis |
|
Definition
| Splenomegaly (due to extramedullary hematopoiesis); Bone Marrow Early in Ds Process - hypercellular with bizzare (large) megakaryocytes; Bone Marrow Late in the Ds Process - Hypocellular with fibrosis; Leukoerythroblastic blood smear (immature white cells, immature nucleated red cells and tear-drop shaped mature erythrocytes) |
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Term
| Leukoerythroblastic Smear |
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Definition
| Neucleated red cells, Immature white cells (myelocytes, metamyelocytes), Tear-drop shaped erythrocytes; DDx - myelofibrosis, space-occupying lesion |
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|
Term
| Clinical Features of Myeloid Metaplasia with Myelofibrosis |
|
Definition
| Uncommon before age 60; Often preceded by myeloproliferative disorders (P.vera or CML), those cases that are not preceded by CML or P.vera are known as Agnogenic Myeloid Metaplasia (AMMF); Marked splenomegaly |
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Term
| Essential Thrombocythemia |
|
Definition
| The least common of the myeloproliferative disorders; Megakaryocyte proliferations; Increased platelets (thrombocytosis); Thrombosis; Hemorrhage |
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|
Term
| Myeloproliferative Disorders all involve proliferation of granulocytes, red cells and megakaryocytes, how do you differentiate between the diseases? |
|
Definition
| Based on which of the elevated myeloid cells are the MOST elevated: CML - granulocytes, P.Vera - erythrocytes, Essential Thrombocythemia - megakaryocytes/ platelets |
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|
Term
|
Definition
| A genetic mutation seen in P.vera, Agnogenic Myeloid Metaplasia (AMMF), and Essential Thrombocythemia; Most closely associated with P.vera |
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|
Term
| Most Common Causes of Anemia |
|
Definition
| Acute Blood Loss (GI bleed, traumatic bleed, AAA rupture), Iron Defficiency (subacute), Chronic Disease (renal, liver, infection, inflammatory, granulomatous, collagen vascular, and others); These 3 things (Acute blood loss, iron deficiency, and chronic disease states) account for about 75% of all anemias |
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Term
|
Definition
| Pallor of the skin, mucous membrane, conjunctiva, nail beds and palmar creases (Hg <8mg/dl); Tachycardia (HR >100); Heart murmurs; Angina pectoris (ischemic chest pain); Exertional dyspnea (exercise induced shortness of breath - especially pronounced with background COPD); Smooth, sore or beefy red tongue; Cheilosis (dry, scaling, fissuring of lips); Koilonychia (spoon-shaped nails); Fatigue and malaise; Postural hypotension |
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Term
| In which disorder might you see Ataxia, Loss of position and vibratory senses and Hyper-reflexia? |
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Definition
| B12 deficiency (due to its demyelinating features) |
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Term
| In which disorders might you see Jaundice? |
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Definition
| Any of the Hemolytic anemias |
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|
Term
| What is Pagophagia and in Which disorder might you see it? |
|
Definition
| Eating of ice; Seen in Iron-deficiency |
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Term
| Which disorders would show abnormal lab values for Lactate Dehydrogenase and or Haptoglobin? |
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Definition
| Hemolytic Anemias (increased LDH, decreased haptoglobin) |
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Term
| What are the 3 main Labs you want when working up a patient for suspected iron deficiency anemia? |
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Definition
| Iron, Total Iron Binding Capacity (TIBC), and Ferritin (only rarely will you get a transferrin level); If the patient has iron deficiency anemia, the will have decreased iron and ferritin and an increased TIBC |
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|
Term
| How much iron is lost from urine, sweat and intestinal mucosa as ferritin each day? |
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Definition
|
|
Term
| How much iron is lost with each day of menstruation? |
|
Definition
|
|
Term
| What is a Normal Hematocrit? |
|
Definition
Women: 40-44%;
Men: 42-52% |
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|
Term
| What is a Normal Hemoglobin? |
|
Definition
|
|
Term
| What is a Normal Mean Corpuscular Volume (MCV)? |
|
Definition
| 80-100; <80 is microcytic; >100 is macrocytic |
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|
Term
| Predisposing Factors for Iron Deficiency Anemia |
|
Definition
| Heavy menstrual bleeding; 4 positive guiac stools (chronic use of NSAIDs, recurrent peptic ulcer disease); Childbearing; Antacids; Tetracycline |
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Term
|
Definition
| Constitutional sxs (weakness, dizziness); Tachycardia; Decreased exercise tolerance (exertional dyspnea); Pallor |
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|
Term
| Transferrin Saturation Ratio |
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Definition
| Iron/ TIBC x 100; If it is less than 15% this is consistent with Iron Deficient Anemia (this ratio helps when ferritin is falsely elevated in a patient with an inflammatory condition as a result of the fact that it's an accute phase reactant); In a patient with Iron Deficient Anemia, you'd expect ferritin to be low, so if it comes back high but you're still suspicious (and iron and TIBC values are as you would expect) this ratio can be a "tie breaker" in your evaluation |
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Term
| S/S of Megaloblastic Anemias |
|
Definition
| Fatigue, exaggerated cardiovascular problems, exaggerated pulmonary problems, sore smooth tongue, CNS affects (in B12 deficiency) |
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|
Term
| How much B12 does the typical western diet contain? |
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Definition
|
|
Term
| How much B12 does the average person lose each day? |
|
Definition
|
|
Term
| How long does it take symptoms of B12 deficiency to develop? |
|
Definition
| 3-4 years because that's how long it takes to depleat your stores (total body stores range from 2000 to 5000 ug, much of which is stored in the liver, and the average person only loses 1-2ug/day) |
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Term
| Which populations are at increased risk of Inherited Atrophic Gastropathy? |
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Definition
| Northern Europeans (Swedish, Scandanavian); Inherited Atrophic Gastropathy is one of the causes of B12 deficient anemia becuase of reduced IF and HCl secretion |
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|
Term
| Triad of B12 Deficiency Symptoms |
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Definition
| Weakness and/ or dyspnea; Sore tongue; Symmetric numbness or tingling in extremities (stocking/glove neuropathy) |
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|
Term
| Importance of Testing for Methylmalonic Acid Levels in a person with Borderline B12 levels |
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Definition
| Normal B12 levels are 200-1000; In someone with s/s of B12 deficiency but who has a technically normal B12 level (ex: 250), measuring methylmalonic acid levels may assist in differentiating if B12 deficiency exists (if it's increased, they have B12 deficiency, even if their B12 level is in the normal range) |
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|
Term
| Demographics of Pernicious Anemia |
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Definition
| Northern European descent; Occurs equally in both sexes; Average age of onset is 60 |
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Term
|
Definition
| Painful red tongue; Loss of vibratory sense; Tingling and paresthesias; Vertigo; Emotional Instability; Disorientation and confusion; Muscle weakness |
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Term
| Why should you check for Hypothyroidism in patients with Pernicious Anemia? |
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Definition
| Because patients with antibodies against the gastric mucosa often also have antibodies against the thyroid |
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|
Term
| How much Folate is in the American diet? |
|
Definition
|
|
Term
| How much Folate do Humans Require? |
|
Definition
| 3ug/kg/day (minimum daily adult requirement is 210 ug for the average 70kg individual) |
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|
Term
| In Which Conditons are Folate Requirements Increased? |
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Definition
| In conditions of high metabolic rate or increased rate of cell division: Pregnancy (16ug/kg/day or 1mg/day), Lactation (400 to 800 ug/day), Infection, Malignancies, Hemolytic Anemias |
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|
Term
| How long does it take symptoms of Folate deficiency to develop? |
|
Definition
|
|
Term
| Predisposing Factors for Folate Deficient Anemia |
|
Definition
| Alcoholism (restricted intake, toxic liver and intestinal effects); Rapid cell turnover (folate is required for most metabolic pathways) - hemolytic anemias, hemoglobinopathies, leukemias, lymphomas, multiple myelomas; Dietary Deficiencies (food faddism); Pregnancy; Diseases that impair absorption from the small intestine; Drugs that alter folate metabolism or absorption (trimethoprim, pyrimethamine, methotrexate, sulfasalazine, oral contraceptives, anticonvulsants) |
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Term
| What are the 3 Factors responsible for Anemia of Chronic Disease? |
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Definition
| 1) Impaired release of iron from reticuloendothelial stores; 2) Decreased erythrocyte life span; 3) Inadequate bone marrow response to a decreased erythrocyte life span |
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Term
| What are normal levels of Erythropoietin? |
|
Definition
| 10-20 IU/L; In anemia of chronic disease, it's not uncommon to see levels of 200-500 IU/L (unless the chronic disease causing AOCD is renal disease, in which case epo levels would be low because the kidneys aren't making it) |
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Term
| Therapy for Anemia of Chronic Disease |
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Definition
| Administration of human recombinant erythropoietin may be indicated for use in anemia associated with: end-stage renal disease, AIDS, cancer, drug-induced anemia (chemo, zidovudine) |
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Term
| With which disorder is there commonly a lack of response to Erythropoietin? |
|
Definition
| Iron deficiency; This is becuase the ability of EPO to stimulate the production of RBCs is highly dependent on the availability of functional iron |
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|
Term
| Why is there a Black Box Warning on Erythropoietin? |
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Definition
| Because you shouldn't try to bring the Hg all the way back up to normal (14-18), you should just try to get it in the 10-12 range or people will develop DVTs |
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|
Term
| What should you do if Folate levels appear normal in the blood, but you're still suspicious the patient has a folate deficiency? |
|
Definition
| Get a RBC Folate level (it's more specific, and less sensitive to recent dietary changes in folate intake) |
|
|
Term
| What should you do if B12 levels look normal, but you're still suspicious that the patient has a B12 deficiency? |
|
Definition
| Get a serum methylmalonic acid level |
|
|
Term
| What are the 3 big indicators of Iron Deficiency? |
|
Definition
| Decreased Iron, Increased TIBC, Decreased Ferritin |
|
|
Term
| If you're checking folate, what else should you automatically check? |
|
Definition
| B12 - because if B12 deficiency is really the problem, it may be masked by administering folate (i.e. the s/s of anemia will improve), but since you're not treating the real problem, you can still develop the demyelination |
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|
Term
| What is the Purpose/ Goal of primary hemostasis? |
|
Definition
| Formation of a platelet plug - involves the vascular endothelium, vonWillenbrand factor (vWF) and platelets |
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|
Term
| What is the Purpose/Goal of Secondary Hemostasis? |
|
Definition
| Formation of a fibrin net to stabilize the platelet plug formed in primary hemostasis. |
|
|
Term
| What is Adhesion (in Primary Hemostasis)? |
|
Definition
| Binidng of vWF to platelets - Specifically, it is the Glycoprotein Ib (GPIb) on the platelets binds to vWF; If a patient is lacking GPIb (a condition known as Bernard-Soulier) they are "tipped toward bleeding" since they can't bind platelets to vWF and can therefore not for a platelet plug |
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|
Term
| What is Aggregation (in Hemostasis)? |
|
Definition
| Fibrinogen (AKA Factor I) has 2 mirror image sets of alpha, beta and gamma chains which results in 3 Domains: D--E--D. The D domains of fibrinogen have a high affinity for the Glycoprotein IIbIIa (GPIIbIIIa) receptor on platelets. Since each fibrinogen molecule has 2 D domains, each fibrinogen can bind to 2 platelets. In addition, each platelet has multiple GPIIbIIIa receptors and can bind to more than one fibrinogen molecule at a time. The result is aggregation of platelets and fibrinogen at the site of a cut in the vascular endothelium. If a patient is lacking GPIIbIIIa (a condition known as Glanzmann's thrombopenia) they are "tipped toward bleeding" |
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|
Term
| What is another name for Factor 1? |
|
Definition
| Fibrinogen (Factor 1a - activated factor 1 - is known as fibrin) |
|
|
Term
| What is another name for Factor 2? |
|
Definition
| Prothrombin (Factor 2a- activated factor 2 - is known as thrombin) |
|
|
Term
| What Are the Clotting Factors of the Common Pathway? |
|
Definition
| 10, 2 (Prothrombin), 1 (Fibrinogen) and 1a (Fibrin) |
|
|
Term
| What are the Clotting Factors of the Intrinsic Pathway? |
|
Definition
|
|
Term
| What are the Clotting Factors involved in the Extrinsic Pathway? |
|
Definition
|
|
Term
| The Intrinsic Pathway is just a test-tube artifact, what happens in vivo? |
|
Definition
| Factor 7 (of the extrinsic pathway) activates factor 9, which goes (via factor 8) on to activate factor 10 and then down the common pathway |
|
|
Term
| What is Clotting Factor 6 thought to be? |
|
Definition
|
|
Term
| What is the role of Clotting Factor 2? How does this cascade down to polymerization of Fibrin? |
|
Definition
| Once it is activated by Factor 5, it becomes factor 2a, which then converts fibrinogen (Factor 1) into fibrin (Factor 1a) by cleaving off fibrinopeptide A (FPA) and fibrinopeptide B (FPB) - onces FPA and FPB have been cleaved off, the D domain of fibrin is attracted the the E domains of neighboring fibrin molecules and vice versa - this causes polymerization of fibrin molecules via ionic bonds, forming a "net" |
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|
Term
| What is the role of Factor 13? |
|
Definition
| Once the fibrin net has initially been formed (ionic bonds between D and E domains of neighboring molecules) it is not especially strong. Factor 13 comes through and forms covalent bonds between adjacent D domains to stabilize things. The fibrin net is then laid down over the platelet plug formed during primary hemostasis and tacks it down. |
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|
Term
| Why is Fibrinolysis important? |
|
Definition
| In tissues without a lot of collateral circulation, you don't want the clot formed during hemostasis to overgrow and completely occlude the vessel (similarly, you don't want clots to grow beyond the area of the vascular endothelial damage), so fibrinolysis breaks down the clot once fibrin has been laid down and collagen begins to re-grow |
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|
Term
| What is involved in Fibrinolysis? |
|
Definition
| Plasminogen is converted to plasmin by Tissue Plasminogen Activator (tPA). Plasmin works to split the fibrin up into fibrin degredation products: D, E and D-D (i.e. D-dimer) domains. D-dimers remain connected because plasmin is unable to break the stable covalent bond created by factor 13. |
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|
Term
| What 2 Molecules stand in the way of Fibrinolysis? |
|
Definition
| Alpha-1-AntiPlasmin (acts against plasmin), and Plasminogen Activator Inhibitor (PAI) which is an acute phase reactant that acts against tPA - inhibiting tPA stops the conversion of plasminogen to plasmin and without plasmin, clots are not dissolved |
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|
Term
| What will you see Clincally in someone with a Defect in Primary Hemostasis? |
|
Definition
| Immediate bleeding after an injury; Mucocutaneous bleeding (bruising, nose-bleeds which may be severe, menorrhagia, and/ or GI bleeds) |
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|
Term
| What will you see Clincally in Someone with a Defect in Secondary Hemostasis? |
|
Definition
| Bleeding which resumes hours to days after an injury; Bleeding into joints and/or muscles |
|
|
Term
| What does Bleeding Time test? |
|
Definition
|
|
Term
|
Definition
| The functioning of the extrinsic pathway; NOTE - PT is the shorter of the two measures of hemostasis (aPTT being the other) and the extrinsic pathway is the shorter of the 2 pathways |
|
|
Term
|
Definition
| The functioning of the intrinsic pathway; NOTE - aPTT is the longer of the two measures of hemostasis (PT is the other), and the intrinsic pathway is the longer of the 2 pathways |
|
|
Term
| What is the normal range for a PT? |
|
Definition
| 11-13 seconds (average = 12); On warfarin the level is more in the range of 24-36 seconds |
|
|
Term
| What is the normal range for an aPTT? |
|
Definition
|
|
Term
| What is the normal range of an INR? |
|
Definition
|
|
Term
| vonWilenbrand Disease (vWD) |
|
Definition
Autosomal Dominant; 3 Types: 1) Type I - the most common (80%), a quantitative defect in vWF (only 50% of the normal amount is produced), 2) Type II - 18% of cases, qualitative defects in vWF (they're too short to reach into the lumen and find platelets), 3) Type III - 3% of cases, a quantitative defect in vWF (less than 5% of the normal amount is made);
S/S = due to the fact that it's a disorder of primary hemostasis - immediate bleeding, mucocutaneous bleeding |
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|
Term
| What is the relationship between vonWilenbrand Factor (vWF) and Factor 8? |
|
Definition
| vWF binds factor 8 (factor 8 doesn't survive by itself) - so in quantitative defects of vWF (ie Types I and III vonWilenbrand Disease), you will also see a decrease in the amount of factor 8 (this will result in an increase in the aPTT since factor 8 is a part of the intrinsic pathway) |
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|
Term
|
Definition
| Sex-linked recessive; Factor 8 Deficiency; Accounts for 80% of all Hemophilia cases; Can be mild (6-30% of normal levels of factor 8) which may be asymptomatic, to severe (less than 1% of the normal amount of Factor 8) in which case patients may bleed spontaneously. |
|
|
Term
|
Definition
| Sex-linked Recessive; Accounts for 18% of Hemophilia cases; Factor 9 deficiency |
|
|
Term
|
Definition
| Autosomal; Accounts for less than 2% of Hemophilia cases - Mostly seen in Ashkenazi Jews; Factor 11 deficiency |
|
|
Term
| Presentation of Hemophilia |
|
Definition
| Involves Clotting factors, so it's part of secondary hemostasis and you'll see S/S consistent with that - delayed bleeding and bleeding into joints and/ or muscles |
|
|
Term
| What Are the Vitamin K Dependent Proteins? |
|
Definition
| Clotting Factors 2,7,9, and 10, and Proteins C and S; All of these are serine proteases with a binding zone and glutamic acids, vit. K gives the glutamic acids additional negative charges via gamma-carboxylation |
|
|
Term
| What is the purpose of Gamma-carboxylation of the vitamin k dependent proteins by vit. K? |
|
Definition
| The proteins then have a negative charge. Since platelets also have a negative charge calcium is required to join the two together so that each clotting factor can be brought into close enough proximity with the argenine on the next clotting factor down the line (so that that second clotting factor can be activated). Factor 8 holds Factors 9 and 10 near each other, while factor 5 holds Factors 10 and 2 near each other; Note - factors 8 and 5 are not vitamin K dependent proteins. |
|
|
Term
| How Does Warfarin/ Coumadin Act? |
|
Definition
| In the process of gamma-carboxylating vitamin k dependent proteins, vitamin K itself is oxidized, rendering it inactive. Normally, 2 enzymes recycle it back to its reduced state. Warfarin/ Coumadin blocks these enzymes so that vitamin K remains inactive. Without vitamin K, there is no gamma-carboxylation and thus the clotting factors cannot be held to the platelet plug and cannot be brought near enough to each other to activate the next one down the line in the clotting cascade, so the patient is "tipped toward bleeding" |
|
|
Term
| Why will you see changes in the PT/ INR before changes in the aPTT in a patient on Warfarin? |
|
Definition
| Because PT and INR measure the extrinsic pathway which involves factor 7, and factor 7 has the shortest half-life of any of the clotting factors. |
|
|
Term
| Where does Vitamin K come from? |
|
Definition
| It is found in Leafy, green vegetables and it is produced by some natural gut flora |
|
|
Term
| Where are the clotting factors made? |
|
Definition
| In the liver (with the possible exception of factor 8 - the current theory is that it is synthesized by blood vessels located in the liver, but not by the liver itself and not by any vessels outside the liver); So, if the liver starts to fail, the level of clotting factors will start to fall (with factor 7 levels falling first since it has the shortest half-life) |
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|
Term
| What happens to D-Dimer levels in a patient with Liver disease? |
|
Definition
| D-dimer levels go up, because the liver clears many things (including activated enzymes such as plasmin); Tips the patient toward bleeding |
|
|
Term
| What Happens to Factor 8 levels in a patient with Liver Disease? |
|
Definition
| It goes up because liver disease is often an inflammatory process, and inflammatory processes increase factor 8 (because it's an acute phase reactant???); Increased factor 8 tips patients toward bleeding (which is reflected by an increased aPTT seen in patients with liver disease) |
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|
Term
| What is the Pathogenesis of Disseminated Intravascular Coagulopathy (DIC)? |
|
Definition
| Patients form clots everywhere in their body; They are consuming all of their clotting factors and fibrinolysis is increased as well - this is basically a vicious cycle - the patient is bleeding from everywhere (because of the increased fibrinolysis), but they're also in multi-system organ failure because their organs aren't getting enough blood due to the fact that the vessels supplying them have clotted off |
|
|
Term
| What are the Clinical Settings Associated with DIC, and what do they have in common? |
|
Definition
Clinical Settings - Sepsis, obstetrical accidents, trauma (especially head trauma and crush injuries), shock, some cancers (you may see chronic/ compensated DIC in these patients with normal lab values except for an elevated D-dimer), and snake bites;
In Common - tissue factors (amniotic fluid, brain, etc.) getting into the blood (ex: there's lots of thromboplastin in the brain and amniotic fluid) |
|
|
Term
| What is the Role of Antithrombin? |
|
Definition
| It "mops up" thrombin so that you don't continue to clot when you no longer need/ want to; Antithrombin needs heparin sulfate (located on intact vascular endothelium) in order to work; Without antithrombin you form clots (causes 2-4% of hereditary thrombophilia) |
|
|
Term
| What is the role of Thrombomodulin? |
|
Definition
| It pulls the thrombin out of circulation so that it can't activate platelets or factors 5, 13 or 8; Thrombomodulin is located on the vascular endothelium |
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|
Term
| What is the result of Factor 5 (Leiden) Deficiency? |
|
Definition
| Clotting Disorder; You would think it would result in a bleeding disorder since factor 5 is involved in clotting, however... Factor 5 has 2 sites on it - one on which thrombin acts to turn Factor 5 ON (leading to clotting) and one one which protein C acts to turn factor 5 OFF (stopping the clotting); In factor 5 deficiency an A at the protein C site becomes a G and protein C can no longer turn factor 5 OFF (but, thrombin can still turn it ON - so you still get clotting) |
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|
Term
| What is the hallmark of Hemolytic Anemia? |
|
Definition
| Elevated reticulocyte count in the setting of anemia (this is a compensatory response to premature loss of erythrocytes); The only other condition that causes anemia with reticulocytosis is acute bleeding |
|
|
Term
|
Definition
| (aa/a_); Clinically normal |
|
|
Term
|
Definition
| (a_/a_) or (aa/_ _); Clinically normal, but may have mild anemia and decreased MCV |
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|
Term
|
Definition
| A form of Alpha Thalassemia; (a_/_ _); Moderate to severe lifelong hemolytic anemia, splenomegaly, bone changes and ineffective erythropoiesis |
|
|
Term
|
Definition
| AKA Beta Thalassemia Major (no effective production of beta chains); B+/B+ or B0/B0 |
|
|
Term
| What happens to babies born with beta thalassemia? |
|
Definition
| They are well at first because of the production of fetal hemoglobin (2alpha chains and 2 gamma chains); As HbF levels decline, patients develop hemolysis anad ineffective erythropoiesis |
|
|
Term
|
Definition
| A clinical feature seen in Beta thalassemia (skeletal abnormalities result because ineffective erythropoiesis causes abnormal skeletal development) |
|
|
Term
|
Definition
| Infection with Yersinia enterocolitica is a significant cause of morbidity in patients with thalassemia and other iron overload syndromes, such as chronic liver disease and hereditary hemochromatosis; Yersinia enterocolitica is siderophilic (iron is essential for its growth), so patients with iron overload provide a perfect environment for Yersinia enterocolitica |
|
|
Term
| Clinical Features of Beta Thalassemia |
|
Definition
| Profound growth retardation; Delayed sexual development; Gouty arthritis/ nephropathy; Cardiac malfunction, including congestive heart failure and fatal arrythmias, frequent causes of death; Cardiac dilation secondary to anemia is nearly universal - improves with transfusion, untreated leads to end-stage cardiomyopathy |
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|
Term
| What is a Test for Sickle Cell Anemia used in the Emergency Setting? |
|
Definition
| Sickledex - it's a 5 minute solubility test used to detect the presence of HbS; It is of little diagnostic value though because it doesn't differentiate between sickle syndromes and the benign carrier state |
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|
Term
| What is different about Osteomyelitis in patients with Sickle Cell Disease (SCD) vs. Osteomyelitis in patients without SCD? |
|
Definition
| Osteomyelitis is most commonly caused by Salmonella in patients with SCD; In the general population, osteomyelitis is most commonly caused by Staph |
|
|
Term
|
Definition
| Seen in 30-50% of patients with Sickle Cell Disease; Clinical S/S include chest pain, new infiltrate on chest x-ray and fever; Most frequent cause of death in adults with SCD; Etiology is thought to be vaso-occlusion, but infarction, embolism, and pneumonia need to be considered |
|
|
Term
|
Definition
| Currently in widespread use to stimulate HbF production in patients with Sickle Cell Disease |
|
|
Term
|
Definition
| Related to Sickle Cell and HbS; Homozygous HbC is usually clinically silent; HbSC is less symptomatic than HbSS, but common problems include Retinopathy and Splenomegaly (increased risk of sequestration crisis) |
|
|
Term
| Paroxysmal Nocturnal Hemoglobinuria (PNH) |
|
Definition
| Involves a defect in the ability to synthesize the membrane glycan-phosphatidylinositol anchor that stabilizes decay accelerating factor (DAF) - this defect makes RBCs susceptible to complement-mediated lysis; Results in episodic intravascular hemolysis, classically at night; These patients are at an increased thrombotic risk and are at risk of developing myelofibrosis or aplastic anemia |
|
|
Term
| Testing for Paroxysmal Nocturnal Hemoglobinuria |
|
Definition
| Acid Hemolysis (Ham Test), Sucrose Hemolysis (hypotonic medium), CD-59 Negative |
|
|
Term
|
Definition
| Looks for immunoglobulin and/or complement on the surface of RBCs (normally neither one is found on the RBC surface); Coombs Reagent - combination of anti-human immunoglobulin and anti-human complement; Reagent is mixed with patient's RBCs and if immunoglobulin or complement are on the surface, the reagent will link cells together and cause agglutination of RBCs |
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|
Term
|
Definition
| Looks for anti-RBC antibodies in the patient's serum using a panel of RBCs with known surface antigens; Combine the patient's serum with cells from a panel of RBCs with known antigens, add Coombs reagent to this mixture - if anti-RBC antigens are in serum, agglutination occurs |
|
|
Term
| Hemolytic Transfusion Reaction |
|
Definition
| Caused by recognition of foreign antigens on transfused RBCs; Several Types - Immediate Intravascular Hemolysis (occurs in minutes; due to preformed antibodies; life-threatening); Slow Extravascular Hemolysis (occurs in days; Usually due to repeat exposure to a foreign antigen to which there was previous exposure; usually only mild sxs); Delayed Sensitization (occurs in weeks; usually due to first exposure to foreign antigen; asymptomatic) |
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|
Term
|
Definition
| Due to formation of autoantibodies that attack a patient's own RBCs; Type (warm v. cold) is characterized by ability of autoantibodies to fix complement, and the site of RBC destruction; Often associated with either lymphoproliferative disease (ex: CLL) or collagen vascular disease (ex: Lupus, Rheumatoid Arhtritis) |
|
|
Term
| Warm Autoimmune Hemolysis |
|
Definition
| Most commonly involves IgG antibodies; Fix complement only to level of C3, if at all; Immunoglobulin binding occurs at ALL temps; Hemolysis is primarily extravascular; 70% of cases are associated with other illnesses (non-hodgkin's lymphoma, CLL, SLE, HIV); Responsive to steroids, splenectomy, plasmapheresis |
|
|
Term
| Cold Autoimmune Hemolysis |
|
Definition
| Most commonly IgM mediated; Antibodies bind best at 30 degrees or lower; Fix entire complement cascade; Typically only complement found on cells; 90% of cases are associated with other illnesses (HIV, Mono, Lymphoma, Mycoplasma pneumonia); Poorly responsive to steroids, splenectomy; Responsive to plasmapheresis; Stay out of the cold |
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|
Term
| Incidence of Acute Leukemia |
|
Definition
| 9,000-10,000 cases of acute leukemia in the US annually; 1.2% of all cancer deaths; ALL accounts for ~80% of leukemia in children, while AML accounts for ~80% of leukemia in adults; Incidence increases with age |
|
|
Term
|
Definition
|
|
Term
| What are "Sanctuary Sites" in ALL, and why are they a problem? |
|
Definition
| The CNS and Testes; They're a problem because chemo can't get into these places |
|
|
Term
| What are the 3 Phases of Chemo Treatment for ALL? |
|
Definition
| Induction (high dose, used to get the patient into remission); Consolidation (high dose, used to maintain remission); Maintenance (lower dose, used to ensure cure - the chemo may be given for 1-2 years following entry into remission) |
|
|
Term
|
Definition
| Indicates a poor prognosis (it's a good prognostic factor in CML though) |
|
|
Term
|
Definition
| Seen with hyperleukocytosis (WBC>100,000); More typically seen in AML than ALL; Includes blurred vision, cerebrovascular dysfunction, or respiratory distress |
|
|
Term
| What are the Phases of Chemo Treatment for AML? |
|
Definition
| Induction and Consolidation (Maintenance chemo is not indicated because if the patient hasn't responded to induction or consolidation chemo within 4 months, they're probably not going to survive the disease) |
|
|
Term
| All-Trans Retinoic Acid (ATRA) |
|
Definition
| A "fancy" version of vitamin K that can induce remissions in up to 95% of patients with Acute Promyelocytic Leukemia (APML, M3 AML); Treatment with ATRA is then followed by chemo |
|
|
Term
| What is the most common leukemia in Adults? |
|
Definition
| CLL (patients are usually >50 years old, with a median age of 62); 6000 new cases in the US each year |
|
|
Term
| Clinical Presentation of CLL |
|
Definition
| Diagnosed as an incidental finding on routine blood counts in 20% of cases; Sxs of progression include weight loss, fatigue, fever and recurrent infections; PE and Lab abnormalities include adenopathy, hepatosplenomegaly, anemia and thrombocytopenia |
|
|
Term
|
Definition
| Generally indolent with gradual increase in lymphocytosis, adenopathy and splenomegaly; May be years before Rx is required; Occasionally see transformation to ALL, Prolymphocytic Leukemia, or Richter Syndrome (~5% transform to aggressive large cell lymphoma/ leukemia) |
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|
Term
|
Definition
| A CLL variant that usually occurs in the elderly; Associated with massive splenomegaly, marked lymphocytosis (usually greater than 100,000 per microliter) and minimal lymph node enlargement; Peripheral blood reveals larger lymphocytes than are found in classical CLL |
|
|
Term
|
Definition
| Characterized by pancytopenia, massive splenomegaly and accumulation of lymphoid-appearing cells with "hairy" cytoplasmic projections; Bone marrow is often difficult to aspirate ("dry tap") secondary to myelofibrosis and infiltration of hairy cells; Cells typically B cell in origin, stain strongly for tartaric acid-resistant acid phosphatase |
|
|
Term
|
Definition
| 4,000-5,000 new cases diagnosed in the US each year (15-20% of all leukemias); Rare in childhood, median age of diagnosis 50-60 |
|
|
Term
|
Definition
| Chronic (Stable) Phase - excess number of myeloid cells that differentiate normally; Accelerated Phase - Progressive loss of the capacity for terminal differentiation of the leukemic clone, 70-80% risk of blastic transformation; Blast Crisis - Progressive bone marrow failure and rapid clinical deterioration, Transformation may be myeloblastic, lymphoblastic, mixed or rarely monoblastic or erythroblastic, Chemotherapy refractory, median survival 2-3 months |
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|
Term
| Incidence of Non-Hodgkin's Lymphoma |
|
Definition
| ~6th most common cause of cancer death in the US; Increasing in incidence and mortality |
|
|
Term
| Types of Non-Hodgkin's Lymphoma (NHL) |
|
Definition
Indolent (Low-grade) - life expectancy in years if untreated, 85-90% of cases present in stage III or IV, excellent response to treatment, Incurable;
Intermediate;
Aggressive (High-grade) - life expectancy in weeks if untreated, potentially curable |
|
|
Term
| What is the most common low-grade B-cell Neoplasm in Adults? |
|
Definition
| Follicular Center Lymphoma |
|
|
Term
| What is the most common high-grade B-cell neoplasm in adults? |
|
Definition
| Diffuse large B-cell Lymphoma |
|
|
Term
| Etiology of Non-Hodgkin's Lymphoma (NHL) |
|
Definition
Immune suppression (congenital, organ transplant, AIDS, increasing age);
DNA Repair Defects (ataxia telangiectasia, xeroderma pigmentosum, ionizing radiation);
Chronic inflammation and antigenic stimulation (H.pylori inflammation in the stomach, C.psittaci inflammation in ocular adnexal tissues, Sjogren's syndrome);
Viral Causes (EBV - Burkitt's lymphoma, HTLV I - T cell leukemia-lymphoma, HTLV V - cutaneous T cell lymphoma, Hepatitis C and possibly B) |
|
|
Term
|
Definition
| Fever, Night Sweats, and Weight Loss - used in classification of lymphoma (ex: stage IIb) |
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|
Term
| Clinical Features of Non-Hodgkin's Lymphoma |
|
Definition
| Lymphadenopathy, Cytopenias, Systemic Sxs, Hepatosplenomegaly, "B Symptoms" (fever, weight loss, night sweats); Lymphadenopathy can fluctuate or spontaneously remit, especially in low-grade lymphomas; B Symptoms are more common in high-grade lymphomas; Hematogenous spread of disease with no predictable pattern (as opposed to Hodgkin's Disease which does have a predictable pattern); Classic Lymphomas arise in lymph node or bone marrow; Extranodal primary site is more common in high-grade lymphomas; Waldeyer's Ring involvement is frequent in GI Lymphomas |
|
|
Term
|
Definition
| A translocation seen in Follicular Lymphoma (codes for the bcl-2 oncogene) |
|
|
Term
| Chromosome Changes in Burkitt's Lymphoma |
|
Definition
| t(8;14), t(2;8), t(8;22); cc-myc oncogene |
|
|
Term
|
Definition
| Seen in Mantle Cell Lymphoma; Encodes cyclin D1 gene |
|
|
Term
| When and why would you do a Lumbar Puncture as part of Staging of Lymphoma? |
|
Definition
When - in patients with AIDS lymphoma, T-cell Lymphoblastic Lymphoma, or High-grade Lymphoma with positive marrow;
Why - these patients are at high risk of lymphoma meningitis |
|
|
Term
| Ann Arbor Staging of Non-Hodgkin's Lymphoma (NHL) |
|
Definition
| Stage I - 1 lymph node region or structure; Stage II - >1 lymph node region or structure, same side of diaphragm; Stage III - Both sides of diaphragm; Stage IV - Extranodal sites beyond E designation accompanying stages I-III; The Ann arbor staging system was developed for Hodgkin's Disease, which tends to spread along lymph node chains in an orderly fashion; Since NHL often disseminates widely in a blood borne fashion, the Ann Arbor staging system by itself is not as useful for NHL |
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|
Term
| Reasons to Treat Advanced Indolent Lymphomas |
|
Definition
| Constitutional Sxs; Anatomic obstruction; Organ dysfunction; Cosmetic considerations; Painful lymph nodes; Cytopenias; NOTE - in most cases you wouldn't treat NHL if they didn't have one of these reasons, even stages I or II are usually incurable |
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|
Term
| Treatment Options for Early Stage (I or II) Aggressive Lymphomas |
|
Definition
| Potentially Curable, Disseminates through bloodstream early; MUST use systemic chemo (R-CHOP x 6 cycles or R-CHOP x 3 cycles followed by radiotherapy) |
|
|
Term
|
Definition
| R= Rituxan (Rituximab), C = Cyclophosphamide (Cytoxan), H = Hydroxydaunorubicin (Adriamycin), O = Oncovin (Vincristine), P = Prednisone |
|
|
Term
| Treatment Options for Advanced Stage (III or IV) Aggressive Lymphomas |
|
Definition
| Systemic Chemo (R-CHOP), +/- Intrathecal chemo (AIDS patients and CNS involvement), +/- Radiotherapy (spinal cord compression, bulky disease) |
|
|
Term
|
Definition
| An important NHL Subtype; T-cell malignancy; Male adolescents; T-cell variant of T-cell acute lymphoblastic leukemia; Prognosis improving with intensive ALL regimens |
|
|
Term
|
Definition
| An important NHL Subtype; African variety - jaw tumor, strongly linked to EBV infection; In the US <50% is linked to EBV infection; May present as abdominal mass; Most rapidly growing human tumor; Typical chromosome abnormality - C-myc oncogene linked to one of the immunoglobulin genes; High-dose chemo is often curative |
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|
Term
| What is the most rapidly growing human tumor? |
|
Definition
|
|
Term
|
Definition
| Seen with high volume/ rapidly dividing tumors; May or may not be chemo induced; Hypocalcemia; Hyperuricemia; Hyperphosphatemia; Renal Failure; Hyperkalemia; Treatment is Hydration and allopurinol |
|
|
Term
|
Definition
| An important NHL Subtype; Malignant helper T-cells; Affinity for Skin; Can be treated with electron beam radiation, UV light, or topical alkylating agents |
|
|
Term
| Adult T-Cell Leukemia-Lymphoma |
|
Definition
| An important NHL Subtype; Associated with HTLV-I infection; Caribbean, Southeastern US; Hepatosplenomegaly, leukocytosis, lymphadenopathy, skin involvement, lytic lesions of bone, hypercalcemia; May respond to AZT and interferon |
|
|
Term
|
Definition
| An important NHL Subtype; Aggressive lymphomas of B-cell origin; Burkitt's, Burkitt's-Like and Large Cell Immunoblastic Type; Treatment often limited by immune compromise of the patient; Prognosis improved with HAART therapy |
|
|
Term
|
Definition
| An important NHL Subtype; Chronic infection of the stomach by Helicobacter pylori; Localized to the stomach, indolent course; Can be cured in many cases with antibiotics against H.pylori |
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|
Term
|
Definition
| Hodgkin's Disease (Their presence is necessary to make the diagnosis) |
|
|
Term
| Subtypes of Hodgkin's Disease |
|
Definition
| Lymphocyte predominant, Nodular sclerosis, Mixed cellularity, Lymphocyte depleted; Unlike with non-Hodgkin's Lymphoma, in Hodgkin's Disease the histologic subtype does NOT determine how the disease is treated |
|
|
Term
| Epidemiology of Hodgkin's Disease |
|
Definition
| In developed countries, bimodal distribution of patients: young adulthood, and after age 50; More common in affluent families with few siblings; In developing countries, more common in young children |
|
|
Term
| Signs and Symptoms of Hodgkin's Disease |
|
Definition
| Lymph node enlargement, usually cervical or mediastinal; Systemic "B" symptoms are common; Pel-Ebstein Fever (relapsing, high-grade fever that can reach 105-106 degrees, periodicity of 7-10 days. Fever spikes abrupt in onset and resolution); Pain on drinking alcohol; Pruritis; Poor appetite |
|
|
Term
| Clinical Features of Hodgkin's Disease |
|
Definition
| T-cell mediated immune deficiency, even in early stages; Patients are prone to infections (Herpes zoster "shingles" in 1/4 of patients, opportunistic infections are common); Immune defect may persist even after lymphoma is cured; Predictable contiguous spread of disease (cervical nodes to mediastinum or axilla, mediastinum to periaortic nodes or spleen, etc.) |
|
|
Term
| Diagnosis of Hodgkin's Disease |
|
Definition
| Excisional Biopsy of a lymph node; Fine needle aspirate is NOT sufficient to make the diagnosis of Hodkin's Disease |
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|
Term
| Treatment of Limited Stage Hodgkin's Disease |
|
Definition
| Patients with limited stage disease have historically been cured using extensive radiation fields; Extended field radiation has a significant risk of late toxicities; Modern therapy would combine a brief course of chemo with involved field radiation; Often patients who relapse after radiotherapy can be cured by salvage chemo; Combined chemo and radiotherapy is given for bulky mediastinal masses |
|
|
Term
| Late Complications of Hodgkin's Disease |
|
Definition
| High incidence of second malignancies (leukemia in the first 10 years, solid tumors over time); Leukemia in patients receiving alkylating agents or combined chemo/ radation; Lung cancer and breast cancer in patients receiving radiation to the chest (especially high in smokers - 10-100x risk); Hypothyroidism after irradiation of the neck; Constrictive pericarditis and accelerated CAD after radiotherapy to mediastinum; Infertility after use of alkylating agents; Heart failure after Adriamycin |
|
|
Term
|
Definition
| Less common than non-Hodgkin's Lymphoma, more deadly; Average life expectancy 30-36 months; Some patients develop a very indolent form and live for 10+ years; Incurable, but durable remissions with high-dose chemotherapy (bone marrow or stem cell transplantation); Disease of malignant B-lymphocytes; Little similarity to lymphoma in presentation, age at diagnosis, treatment or prognosis; S/S are variable; Approximately 20% of patients have no sxs |
|
|
Term
| Etiology of Multiple Myeloma |
|
Definition
| Unknown; Suggested predisposing factors include: viral infection with human herpesvirus 8 (HHV-8), MGUS (monoclonal gammopathy of undetermined significance) |
|
|
Term
| Epidemiology of Multiple Myeloma |
|
Definition
| Average age at presentation is ~65; Males > Females; Incidence in blacks is twice that of whites; Five-year survival is ~25-30% |
|
|
Term
| Diagnosis of Multiple Myeloma |
|
Definition
| More than 20% plasma cells in the bone marrow (Normal would be <5%); Monoclonal immunoglobulin peak on SPEP (more than 3gm/dL); Presence of Bence Jones protein in the urine (abnormal light chains); Decreased levels of normal immunoglobulins; Lytic lesions on plain films; Cell Surface Markers (CD38, plasma cell antigen and cell surface immunoglobulins); Monoclonality can be demonstrated by immunoperoxidase staining with kappa and lambda antibodies |
|
|
Term
| Clinical Features of Multiple Myeloma |
|
Definition
| Bone marrow failure (anemia, thrombocytopenia, neutropenia); Renal Failure; Bone disease with skeletal destruction (generalized decrease in bone density, and painful lytic lesions which increase the risk of pathologic fracture); Hypercalcemia; Hyperviscosity Syndrome; Recurrent infections; Amyloidosis |
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|
Term
| When is having a Leukoblastic blood smear normal? |
|
Definition
| During the First week of life |
|
|
Term
|
Definition
| Physiology - bilirubin is produced by RBC breakdown, the newborn liver conjugates poorly, Labs - Total/ direct bilirubin levels (T/D); Direct bilirubin = conjugated; Indirect = unconjugated; Common cause of newborn jaundice - increased indirect bilirubin (T/D = 1/0.2), can be physiologic, from breast milk, or RBC destruction; Uncommon cause of newborn jaundice - increased direct bilirubin, from cholestasis (abnormal bile ducts, sepsis, mass) |
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|
Term
| When is a primative megaloblastic blood smear considered normal? |
|
Definition
| Before 1 week of life; Primitive megaloblastic blood formation begins around 18 weeks gestation |
|
|
Term
|
Definition
| Occur in megaloblastic conditions |
|
|
Term
| Stages of Iron Deficiency |
|
Definition
| 1) Decreased iron stores (decreased ferritin); 2) Decreased transferrin saturation; 3) Morphologic changes (anisocytosis, normochromic, normocytic anemia, decreased Hg, decreased MCV, decreased MCHC, thrombocytosis); 4) Bone marrow depletion |
|
|
Term
| Normal Serum Ferritin Levels |
|
Definition
Newborn: 25-100ng/mL;
1st month of life: 200-600;
2-5 months: 50-200;
>5 months: 7-140;
Adult Male: 20-250;
Adult Female: 10-120 |
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Term
| B-Cell Antigen-Independent Development |
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Definition
| Occurs in bone marrow; stem cell --> mature virgin B cell |
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Term
| T-Cell Antigen-Independent Development |
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Definition
| Occurs in the Thymus; stem cell --> mature virgin T-cell |
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Term
| Antigen-Independent Lymphoid Cell Development |
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Definition
| Occurs largely during fetal/ neonatal and childhood periods for both B and T cells. As a result, malignancies of cells derived from antigen-independent development are seen more commonly in kids (except for mature virgin B and T cells - cancer of these (CLL) is usually seen in adults/ the elderly) |
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Term
| B-Cell Antigen-Dependent Development |
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Definition
| Germinal Center Reaction (the purpose of which is to produce antigen-specific plasma cells); Plasma cells of the bone marrow; Memory cells are generated; Tumors of these types of cells are more prevalent in adults |
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Term
| T-Cell Antigen-Dependent Development |
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Definition
| Occurs in lymph node paracortex; Blast transformation (become mature T effector cells, either CD4+ or CD8+); Memory Cells are generated |
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Term
| Acute Nonspecific Lymphadenopathy |
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Definition
| Enlarged, tender, painful nodes (almost always benign/ due to acute infection); Nodes draining sites of acute bacterial or viral infections; Example - strep pharyngitis and cervical adenopathy |
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Term
| Chronic Nonspecific Lympadenitis |
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Definition
| Enlarged, Painless nodes; Nodes draining sites of chronic, low-grade infections; Also see in some drug reactions; Example - proximal adenopathy in a diabetic with a chronic skin infection |
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Term
| Benign Reactive Lymphadenopathy |
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Definition
| Due to systemic infections (EBV, CMV, HIV, Toxo, Hepatitis, influenza, secondary and tertiary syphilis) and also due to autoimmune disorders (SLE, RA) |
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Term
| Malignant Lymphadenopathy |
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Definition
| Primary Malignant Neoplasms (malignant lymphoma - Hodgkin's Disease and Non-Hodgkin's Lymphoma); Secondary Malignant Neoplasms - more common (metastatic carcinoma, metastatic melanoma, or metastatic sarcoma with which nodal involvement is rare because it spreads hematogenously); When a patient has non-tender lymphadenopathy and you've ruled out infection, you have to consider primary or secondary malignant neoplasms |
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Term
| Clinicopathologic Findings of Low-Grade Lymphadenopathy |
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Definition
| Cells show survival advantage (the lymph nodes are enlarged not because the tumors are growing so fast, but because the cells in them aren't dying off); Slow-growing/ indolent; Essentially incurable (chemo doesn't work on these tumors because they're not rapidly dividing); Long survival (4-12 years); May involve marrow at presentation; Many high stage at presentation (doesn't necessarily correlate to prognosis); Elderly are most affected |
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Term
| Small Lymphocytic Lymphoma (SLL)/ CLL |
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Definition
| Elderly; Essentially all B-cell neoplasms; 4% of Non-Hodgkin's Lymphomas; Arises from virgin B cell; 40% have leukemic phase (CLL); Marrow, spleen and liver involved; Essentially incurable with long survival; SLL and CLL are essentially the same thing, the difference is based on the fact that SLL presents with lymphadenopathy, but no peripheral blood involvement, whereas CLL presents with peripheral blood involvement |
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Term
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Definition
| All are B cell neoplasms; Common, 40% of Non-Hodgkin's Lymphomas; tumor cells create pseudofollicles within the node; Elderly; 75% have marrow involvement; Peripheral blood is rarely involved; Associated with BCL-2 oncogene (t(18;14), gene leads to defective apoptosis, so the cells have a survival advantage); Incurable, average 8 year survival |
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Term
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Definition
| B-cell lymphoma; Middle age to elderly; Most aggressive subtype of Low-Grade Non-Hodgkin's Lymphoma; Marrow and blood involvement are common; Average survival 2-6 years; BCL-1 oncogene (t(11;14), over-expression of cyclin D1) |
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Term
| What is the Standard Diagnostic Imaging for Lymphoma? |
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Definition
| CT scan; Contrast enhanced to distinguish nodes from vessels |
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Term
| What is the Pathologic Criteria for Nodal Size? |
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Definition
| >1cm in short axis (shortest dimension) is considered pathologic; Remember though - enlarged nodes are a non-specific finding (infection, inflammation, neoplasm are all possible causes for lymphadenopathy) |
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Term
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Definition
| 18FDG (fluorodeoxyglucose) is injected into the patient and the isotope is taken up by metabolically active cells and trapped inside, the emitted x-ray photons are then detected by camera; You can calculate the SUV (standard uptake value) to assess for the likelihood of malignancy (>2.5 is suspicious for malignancy); PET scan images can be fused with CT for better localization; PET scans are primarily used in the setting of lymphoma to assess response to treatment |
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Term
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Definition
| Involvement of sites other than lymph node (solid organs); More common in non-Hodgkin Lymphoma than in Hodgkin's (20-40% vs 4-5%); Common with recurrent disease and AIDS (non-Hodgkin Lymphoma is the most common AIDS-related malignancy); Contrast enhanced CT is the preferred imaging modality for staging, extent of organ involvement, assessment of nodal disease and response to therapy |
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Term
| Post-Transplant Lymphoproliferative Disorder (PTLD) |
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Definition
| Nodal or extra-nodal disease; Seen in 2-5% of cases of organ transplant; 80% of cases have extranodal disease |
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Term
| What Solid Organs are Most Commonly Involved in Lymphoma? |
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Definition
| Spleen, Liver, Kidneys, Pancreas, Adrenal Glands, Testes (which are difficult to treat due to the blood/testes barrier which chemo cannot cross); Rarely involves the uterus, prostate, or ovaries |
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Term
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Definition
| Secondary involvement in non-Hodgkins and Hodgkin's lymphoma is common; Primary splenic lymphomas are rare; Diffuse, uniform infiltration is the most common form of splenic lymphoma; Splenomegaly may occur (but is not diagnostically significant); Presence of enlarged perihilar nodes is suggestive of infiltration in the absence of discrete nodules; Multiple nodules may be seen (fungal infection may have the same appearance, difficult to distinguish, systemic cultures are necessary) |
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Term
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Definition
| Primary hepatic lymphoma is very rare (occurs most commonly in immunocompromised patients); Secondary involvement of liver is common in advanced stages of lymphoma (more common in non-Hodgkin's); At presentation, 15% of non-Hodgkin's patients have hepatic involvement; Almost always occurs with splenic disease (b/c of the circulation) - the more extensive the splenic disease, the more likely you are to have hepatic involvement; Diffuse infiltration is the most common appearance and is easily overlooked due to liver normally appearing heterogeneous; Discrete nodules are seen in 10% of cases of hepatic disease (more common in secondary disease); Dominant masses seen in primary hepatic lymphoma (rare in secondary disease) |
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Term
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Definition
| Primary renal lymphoma is rare; Secondary involvement is seen late in the disease; Non-Hodgkin's >> Hodgkin's; 7-14% of non_hodgkin patients develop renal lymphoma; Diffuse infiltration in ~20% of cases; May manifest only as renal enlargement; Most common appearance is multiple low-density masses (commonly bilateral, ~1-3 cm in size); May appear as peri-renal soft tissue masses (surrounds but doesn't invade the kidneys); Gerota's Fascia (the fascia around the kidney) may appear thickened; Biopsy may be necessary |
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Term
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Definition
| Adenocarcinoma tends to arise from mucosa, but lymphoma arises from and extends along the submucosa or deep mucosal layer so it may be missed at endoscopy and if it is seen on CT, the radiologist myst alert the endoscopist of the area to biopsy; CT scan with IV and oral contrast is used and GI lymphoma will appear as thickened walls of stomach or bowel, luminal constriction or dilation, +/- bulky regional adenopathy; Nodular Form - nodular thickening of involved segment, variable sizes of nodules; Polypoid form - most common in stomach, one or more smooth polypoid masses in lumen; Infiltrative Form - focal or diffuse wall thickening, may impair peristalsis due to autonomic plexus damage, may extend into mesentery |
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Term
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Definition
| Most common site of GI lymphoma; 3-5% of all gastric malignancies; Secondary disease > primary; Non-Hodgkin's >> Hodgkin's; Involves all portions of the stomach with equal prevalence; 50-70% of primary cases are MALT lymphoma (associated with H.pylori, may regress with abx, may progress to high-grade B-cell Non-Hodgkin's lymphoma); Dx may not be possible on imaging (bx is normally required); Thickened rugal folds is the most common thing you'll see |
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Term
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Definition
| 2nd most common site of GI lymphoma; 20% of all malignant small bowel tumors; Non-Hodgkin's > Hodgkin's; Hodgkin's is rare to see here - presents as sprue like syndrome with steatorrhea; Usually occurs as a solitary leasion; Believed to occur equally in all sites of the small bowel; Wall thickening (May mimic Chron's ds when isolated to terminal ileum, a colonoscopy with bx may differentiate) |
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Term
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Definition
| Secondary pancreatic involvement in 30% of patients with Non-Hodgkin's Lymphoma; Primary involvement is uncommon; Involvement in Hodgkin's is rare; Diffuse involvement causes enlargement and peripancreatic fat infiltration (may resemble acute pancreatitis) |
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Term
| Adrenal Glands and Lymphoma |
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Definition
| Adrenal involvement is rare; Non-Hodgkin's > Hodgkin's; 4% of Non-Hodgkin's patients; 50% bilateral; May present with adrenal insufficiency; Non-specific imaging appearance (U/L or B/L adrenal enlargement, associated with retroperitoneal adenopathy, other extranodal sites) |
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Term
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Definition
| 5% of testicular tumors are lymphoma; Most common testicular tumor in patients >60 yo; Non-Hodgkin's disease > Hodgkin's; 40% bilateral; May be the only site of disease or one of multiple sites; Involves the body of the testes (spares the tunica vaginalis); Epididymus and spermatic cord are often involved; Ultrasound is the preferred imaging modality; Well defined hypoechoic (dark) areas seen in testes; Testes are often enlarged |
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Term
| Zevalin Treatment of Lymphoma |
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Definition
| Y-90 labeled ibritumomab tiuxetan (Trade name Zevalin) - an anti-CD20 monoclonal antibody; Step 1 - inject In-111 labeled Zevalin 1 week prior to treatment to show biodistribution of antibody; Step 2 - Then inject Y-90 labeled antibody for treatment (it's a beta emitter, treats nodes that express CD20 and become bound to isotope) |
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Term
|
Definition
| Should only be considered as a dx in a patient >40 years; Typically has a diffuse permeative appearance (can mimic Ewing Sarcoma but Ewing's occurs in children so they are not part of the same DDx); Frequently involves the calvarium (Skull); Lytic "moth eaten" appearance (not blastic/ sclerotic); One of the only lesions that is NOT characteristically "hot" on a bone scan (because bone scans show increased osteoblast activity, and myeloma involves increased osteoclast activity) |
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Term
|
Definition
| For evaluation of nodal drainage of malignancy (breast CA prior to mastectomy or lumpectomy, Melanoma prior to excision); 99mTc labeled Sulfur Colloid is injected around the lesion/ nipple (VERY painful); Images are take in frontal and lateral planes following injection and the node is marked; Procedure identifies the first node (sentinel node) in the drainage chain for surgical sampling at excision; Helps in diagnosing nodal metastasis; Can also use gamma probe in the OR to detect if ID is difficult (like a Geiger Counter) |
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Term
| Modalities for Imaging of Infection |
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Definition
CT SCAN with contrast initial preferred imaging for: abd, pelvis, brain (abscess), extremities for soft tissue infection/abscess, CAN'T give contrast in renal failure or with severe allergy, CAN use to guide drainage;
LABELED WBC Studies: WBCs tagged with radioactive Indium, no IV contrast so it's OK for patients with renal failure, poor anatomic detail due to decreased spatial resolution of nuclear medicine imaging, can exclude infection or give general area of involvement; BONE SCAN: osteomyelitis - x-rays are negative for several weeks until bony destruction occurs, poor anatomic detail, in the real world MRI is a better test but boards like Bone Scan;
MRI: osteomyelitis, myositis, necrotizing fasciitis, discitis, epidural abscess, meningitis/ventriculitis, it's a long exam (so claustrophobia or pain may interfere), expensive, CAN'T get with pacemakers, certain metallic devices/ hardware, cochlear implants, intra-orbital metal (metal workers, etc.) |
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Term
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Definition
| Non-contrast CT will show low density areas within parenchyma (may have similar appearance to an infarct, but abscesses will enhance following administration of IV contrast while infarcts do not); Better parenchymal detail with MRI (shows more subtle associated edema, can help differentiate abscesses from tumors); When evaluating abscesses you typically start out with CT without and with contrast and if there is any question of neoplasm then you obtain an MRI; MRI contrast (gadolinium) is much safer than CT contrast, renal insufficiency is not as big a deal and allergies to it are very rare because it's not iodine based unlike CT scan contrast |
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Term
|
Definition
| Meningitis may not always be readily apparent clinically and CSF sampling may not reveal organisms if abx have already been started, so in some cases MRI with contrast may be useful - it will show meningeal enhancement with gadolinium (bright signal on T1 sequences, diffuse or focal enhancement depending on severity of disease) |
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Term
| Imaging of Intra-abdominal/ pelvis abscesses |
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Definition
| Preferred imaging is contrast enhanced CT; May perform MRI or ultrasound if you are unable to obtain a CT for some reason; Appear as enhancing fluid collections (low density) and may have gas contained inside from anaerobic organisms |
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Term
| Imaging for Osteomyelitis |
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Definition
| Plain films are often negative early on (destruction of bone is seen after a few weeks as lucency at the site of infection); Bone scans are helpful in dx of early osteomyelitis (99mTc labeled diphosphonate is injected and taken up by osteoblasts in areas of hyperemia and active bone remodeling/ healing); 3 Phases - 1)arterial "flow" phase at time of injection, 2)blood pool images, tracer distributed in soft masses (cellulitis would be "hot" during this phase) , 3)3-4 hours after injection, skeletal uptake phase; Osteomyelitis is hot on all 3 phases |
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Term
|
Definition
| Can be performed if you are unable to get CT or MRI (due to renal failure, allergy, claustrophobia, etc.); Remove blood from the patient, spin it down and separate leukocytes, add 111-In and re-inject the leukocytes into the patient, then image them 24 hours later; Shows poor anatomic detail compared to CT or MRI, but it gives a general area of involvement and may be helpful in excluding infection; Activity is limited to liver, spleen, marrow (all normal), and site of active infection/inflammation |
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Term
|
Definition
| Active, brisk GI bleeds can be visualized by endoscopy; Angiography is capable of detecting ACTIVE bleeds at ~1cc/sec (place a catheter into the femoral artery and inject contrast into mesenteric arteries, shows active extravasation of contrast outside of vessels if the patient is bleeding at the time of study); If the bleed is slower than 1cc/sec or if it is an intermittent bleed and not seen by endoscopy, you can do a tagged RBC scan |
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Term
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Definition
| A nuclear medicine tagged RBC scan that can detect GI bleeds at ~0.1cc/sec; You can re-image the patient when they are clinically actively bleeding for up to 24 hours after tagging the RBCs (ex: BRBPR - bright red blood per rectum); Remove blood from the patient, spin it down and separate the RBCs, mix the RBCs with 99mTc and re-inject them into the patient, take continuous images @1min intervals for at least 90 mins; Detects increased activity and follows it through the bowel to ID the source of the bleed |
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Term
| "Hair on End" Imaging Finding |
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Definition
| Due to bone marrow (diploe) expansion in the skull; Associated with Sickle Cell and Thalassemia (if both of these were the answer to a question involving hair on end presentation - which Dr.Kloda said would be cruel to do, but boards might - Thalassemia would be the correct answer because it is MORE associated with that than with Sickle cell); The Hair on End will not appear in the occipital region becuase there is no marrow in that area of the skull |
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Term
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Definition
| So-called because of aggressive behavior and poor prognosis. These, however, are treatable with many long-term remissions and cures; Many arise in the background of a pre-existing immunologic disorder such as Sjogrens, Hashimotos thyroiditis, transplant patients (PTLD) and AIDS; Show "fish flesh" grossly and "starry sky" histologic pattern |
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Term
| General Clinicopathologic Characteristics of High Grade Non-Hodgkin's Lymphoma |
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Definition
| Children and adults affected; Approximately 50% of NHL; Rapid proliferation and growth; May be nodal or extranodal; Marrow and blood rarely involved early (because the large nodes/ rapidly enlarging nodes bring the patient in at an early stage of disease); Associated with immune deficiency; Aggressive, but curable |
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Term
| Diffuse Large-Cell Lymphoma |
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Definition
| The most common subtype of High Grade NHL; 80% are B-cell tumors, 20% are T-cell tumors; 80% occur in adults, 20% occur in kids; Rapidly enlarging mass; 50% arise secondary to immunologic disorders; Usually low stage at presentation; 60% are curable (T-cell forms are usually more aggressive) |
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Term
| Lymphoplastic Lymphoma/ ALL |
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Definition
| A form of High Grade NHL; Most occur in patients <20years old; M>F; 40% of childhood lymphoma; 70% with mediastinal mass; T-cell phenotype; Rapid dissemination to marrow/ blood; Aggressive chemo yields some results/ cure rates; Lymphoblastic lymphoma and ALL involve the same cell of origin/ tumor, the difference is in how the patient presents (Lymphoma - mass/ enlarged nodes, Leukemia - increased WBC count) |
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Term
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Definition
| A type of High Grade NHL; Occurs in children and young adults; B-cell Lymphoma (follicular B blasts; ALWAYS B-cell, like follicular lymphoma and SLL/CLL); 30% of all childhood NHL; Usually extranodal (bowel or jaw are common places); Some cases are associated with EBV; CNS and marrow involvement are common; 2 SUBTYPES - Endemic (African Type): EBV associated, mandibular/maxillary mass; Sporadic Type (USA): Not associated with EBV, Abdominal mass (bowel) most common; 50% long-term survival, Many relapse, T(8;14), C-myc oncogene |
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Term
| Hodgkin's Disease (HD) v. Non-Hodgkin's Lymphoma (NHL) |
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Definition
Nodal Involvement and Spread - contiguous in HD;
Extranodal involvement - can be entirely extranodal in NHL;
Type of Infiltrate - HD has benign inflammatory cells present in response to the malignant Reed-Sternberg cells, while NHL has malignant cells themselves replacing nodes;
Reed-Sternberg Cells - HD only, some NHLs have Reed-Sternberg-Like cells though;
Age Distribution - Bimodal in HD |
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Term
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Definition
| The malignant cell of Hodgkin's Disease; RS cells are required for the diagnosis in all cases of Hodgkin's; They are binucleated, single cytoplasm cells with large nucleoli (classic RS cells); Variant RS cells can have >2 nuclei or they may be mononuclear "lacunar" cells; When diagnosing Hodgkin's - once you find a RS cell, you need to look at the background cells to make sure that they are benign, reactive cells since NHL can have Reed-Sternberg-Like cells (but in NHL the background would be malignant tumor cells and you don't want to be fooled since the treatment and prognosis for HD and NHL are very different) |
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Term
| Diagnosis Of Hodgkin's Disease |
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Definition
| MUST see Reed-Sternberg cells; Reed-Sternberg cells MUST be accompanied by the appropriate cellular background in order to be diagnostic; Background infiltrate - mixture of benign lymphocytes, plasma cells, and eosinophils present in varying numbers, but ALWAYS present |
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Term
| Subtypes of Hodgkin's Lymphoma |
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Definition
| Lymphocyte predominant (5%), Mixed Cellularity (30%, more malignant because more RS cells); Nodular Sclerosing (60%, most common and most treatable); Lymphocyte depleted (5%) |
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Term
| Prognosis of Hodgkin's Lymphoma |
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Definition
| Based on the ratio of RS cells to the inflammatory background elements. The more aggressive subtypes contain larger numbers of Reed-Sternberg cells and less background inflammatory cells |
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Term
| Lymphocyte Predominant Hodgkin's Lymphoma |
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Definition
| 2 Subtypes: Nodular (characterized by "popcorn cells") and classical (normal R-S cells); M>F; <35 years of age; Usually with limited (low stage) disease; Excellent prognosis; Rare R-S cells in a sea of lymphocytes; Probable B cell lineage |
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Term
| Mixed Cellularity Hodgkin's Lymphoma |
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Definition
| Males; Elderly; Aggressive subtype; High stage at presentation; Many typical R-S cells; Fewer reactive cells but mixture of eosinophils, plasma cells, and lymphocytes |
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Term
| Lymphocyte Depleated Hodgkin's Lymphoma |
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Definition
| Males; Elderly; Very aggressive; Poor prognosis; Usually disseminated; Many R-S cells; Rare background inflammatory cells; Fibrosis present |
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Term
| Nodular Sclerosing Hodgkin's Lymphoma |
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Definition
| Most common subtype; Females; Young Adults; Usually presents in early stage 1 or 2; Excellent Prognosis; R-S cell variants predominate ("lacunar cells"); Many background cells; Broad bands of collagen separating the nodules |
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Term
| Plasma Cell Dyscrasias (Definition) |
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Definition
| A group of disorders characterized by a neoplastic proliferation of plasma cells usually with the production of intact immunoglobulin or its fragments. Rarely these proliferations may be nonsecretory |
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Term
| General Characteristics of Plasma Cell Dyscrasias |
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Definition
| Eldery are most affected; Produce monoclonal protein ("M protein"); Clones - so they produce only 1 type of Ig; Lymphadenopathy is generally NOT a feature; Marrow based disease |
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Term
| Examples of Plasma Cell Dyscrasias |
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Definition
| Multiple Myeloma, Waldenstrom's Macroglobulinemia, Monoclonal Gammopathy of Undetermined Significance |
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Term
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Definition
| A plasma cell dyscrasia typically seen in the elderly; Mature B cell; Very aggressive due to tumor cell products (this is what kills them, not the tumors), which are nephrotoxic; Light Chains; OAF (osteoclast activating factor?) - causes osteoclasts to eat up bone which leads to lytic bone lesions; Poor prognosis; These patients get a lot of infections because plasma cells can't fight off infections because they're defective (normal immunoglobulin production is suppressed) |
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Term
| Waldenstrom's Macroglobulinemia |
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Definition
| A type of plasma cell dyscrasia; Related tumor of plasmacytoid lymphocytes; Secretes IgM only; Can lead to Hyperviscosity Syndrome (because IgM is a large molecule and it's being made in high amounts); Hepatosplenomegaly; Adenopathy (unlike with multiple myeloma) and marrow involvement; No lytic bone lesions (also unlike multiple myeloma) |
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Term
| Monoclonal Gammopathy of Undetermined Significance |
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Definition
| Benign but clonal proliferation of plasma cells; Low levels of Ig; Asymptomatic; Light chains absent from urine (unlike in multiple myeloma); <5% plasma cells in marrow; 18% progress to myeloma; Clinical follow-up is essential |
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Term
| 4 Basic Functions of the Lymphatic System |
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Definition
| Fluid Balance; Purification and cleansing of tissues; Defense; Nutrition |
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Term
|
Definition
| From blind endings there are also specialty endings with stromata and lacunae, they form lymph capillaries and go to small collecting ducts with some smooth mm. They look like a series of vessels lined up and embedded in each other creating secondary valves of endothelial folds limiting fluid back up. They grow to larger vessels with thin strips of connective tissue and smooth mm. which go to large ducts and trunks. They travel as a triad with arteriole and venule and vascular pulsations influence lymphatic movement |
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Term
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Definition
| Starts as the cisterna chyli; sits on ALL with the AA on top of it; Passes thru the aortic hiatus and traverses the posterior mediastinum between the aorta and azygos v. passing in front of the phrenic nerve and behind the vagus; At T4 it passes left as it enters the superior aperture of the thorax behind the aortic arch and left of the esophagus, there, it goes laterally across the carotid sheath and arches anteriorly and caudally to terminate in the venous system |
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Term
| Stress and the Lymphatic System |
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Definition
| "The larger lymph vessels contain smooth muscle, which is also innervated by the SNS. The extent of sympathetic innervation suggests that response to stress may hinder optimal digestion of tissues via the lymphatic system." |
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Term
| How Does Lymphatic Fluid Move? |
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Definition
| Via Intrinsic and Extrinsic mechanisms; INTRINSIC - lymphangions (endothelial cell lining has a thin wall with smooth m. in rings, it ends with a valve flap), these contract at regular intervals with a refractory period (contractions are coordinated), the endothelial cells can produce compounds like NO which dilate the lymphangion, they have receptors for NE (constricts), ATP (constricts) and beta adrenergic inhibitory mechanisms like the bronchial lining, they are richly innervated and respond to SNS; EXTRINSIC - skeletal mm. and limb movement, heart and vascular pulsations, respiratory movement, intestinal peristalsis, surface massage (intermittent compression over drainage territory can increase lymph flow time 4x) |
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Term
|
Definition
| Usually clear; Contains proteins, salts and, after a meal, fats; Lymphocytes are the primary cells of lymph and are unique among blood cells in their capacity to continually recirculate between blood and the tissues via lymph; Lymph contains clotting factors; Peripherally it may contain particles of bacteria or viruses before filtration |
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Term
| Estimated Number of Adults and Children NEWLY INFECTED with HIV, 2007 |
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Definition
| 2.7 million (2.2-3.2 million) |
|
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Term
| Adults and Children Estimated to be LIVING WITH HIV, 2007 |
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Definition
| 33 million (30-36 million) |
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|
Term
| Total HIV Cases Worldwide |
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Definition
| 34-46 million adults and 5 million children |
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Term
|
Definition
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|
Term
| Percent of the World Population Living with HIV |
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Definition
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Term
|
Definition
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|
Term
| International HIV Concerns |
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Definition
| Poverty (testing not available, medication too expensive, basic healthcare is unavailable); Unstable Government (refugees complicate aid) |
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Term
| Worldwide Impact of HIV/ AIDS |
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Definition
| Damaging to economic development; AIDS costs more than the yearly profits in some country (the result of this is that HIV patients don't get treated in 3rd world countries because it is just too costly for the country) |
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Term
|
Definition
| 66% in Blacks and Hispanics; 23% in women; 44% Gay Sexual Contact (Males) |
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|
Term
| What is the significance of the fact that the HIV virus is fragile? |
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Definition
| It breaks apart easily and can therefore mutate and, as a result, makes it harder to treat |
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Term
|
Definition
| The presence of the HIV Virus in the individual's body |
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Term
|
Definition
| The presence of HIV virus AND the presence of a defining characteristic/ illness |
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|
Term
| What is the confirmatory test in HIV testing? |
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Definition
| Western Blot (do ELISA first, if it's positive, do a Western blot for confirmation) |
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Term
|
Definition
| Refers to Highly Active Anti-Retroviral Therapy (for HIV/ AIDS); Successful viral eradication by use of multiple drugs in different classes |
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Term
|
Definition
| The use of different, unusual or multiple drug regimes when traditional therapy fails (HIV/AIDS) |
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|
Term
| Categorization of HIV/ AIDS |
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Definition
| HIV: I - CD4>500, II - CD4 200-499, III - CD4<200; SUBCLASS: A - with S/S, B - without S/S, C - AIDS |
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Term
| Acute Retroviral Syndrome |
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Definition
| Looks like the flu, Non-specific findings, so history is very important; Fever (96%), lymphadenopathy (74%), Pharyngitis (70%), Rash (70%), Myalgia/ arthralgia (54%), Diarrhea and Headache (32%), Nausea/ vomiting (27%) |
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Term
| Diagnostic Workup of the HIV Patient |
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Definition
| Initial Workup - CBC, chemistry profile (liver function tests because patients tend to have Hep C too, Renal function tests to determine what therapies they can receive), RPR (syphilis tends to occur in the same populations), CD4, Plasma viral load (HIV PCR RNA); Additional Tests - TB test (TB is becoming epidemic in HIV patients), Hep B and C (immunize patients against Hep B if they're negative), CMV serology; Untreated HIV tends to destroy platelets; Treated HIV patients tend to have macrocytic anemias |
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Term
| Physical Exam of the HIV Patient |
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Definition
| Adenopathy; Presence of Rash/ Skin Changes (Dermatological exam); Eye Exam (CMV retinitis); GU/ STD; Cardiac (attention to intravenous drug abuse effects); Liver (hepatitis); Neuro/Psych; GI (diarrhea and malabsorption) |
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Term
| Monitoring Labs of the HIV Patient |
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Definition
Every 3 months while on meds - PCR-HIV RNA, CBC, CD4, CD8, Chemistry Profile;
Less Frequent - liver functions, Hep B and C serology, Syphilis serology, G6PD, TB test (anergy panel) |
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Term
| Perinatal HIV Prevention Strategies |
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Definition
| 3 Major Factors are Associated with Perinatal Period Risks - Maternal HIV levels, Prolonged rupture of membranes during childbirth, and Breastfeeding when maternal RNA levels are high; One study demonstrated that limited med use during the childbirth phase reduced infant conversion rates from 30% to <1%; Breast feeding when the mother is on meds is successful with less than 2% infection and the meds are cheaper than infant formula |
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Term
| General HIV Prevention Strategies |
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Definition
| Reducing sexual transmission rates; Most important is reducing RNA levels; Circumcision; Barrier use; Avoiding intercourse during activated immune system times (genital herpes, syphilis and gonorrhea) |
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Term
| When Should a Patient Be Started on HIV Treatment? |
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Definition
| Not right away (i.e. not at time of dx); Not if the CD4 count is >350-400; Wait until the patient is ready/ committed because once they start, they can't go off the meds because missing even 2-3 days can induce viral resistance to these drugs and since many of the drugs are so similar, developing resistance to one can translate into resistance to many drugs (and there are only about 20 drugs to begin with, so you could quickly eliminate a huge percentage of treatment options); Use the simplest regimen possible to increase compliance |
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Term
| What are Examples of Reverse Transcriptase Inhibitors (RTI)? |
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Definition
| Atripla, Combivir, Emtriva, Epivir, Epzicom, Retrovir, Trizavir, Videx, Viread, Truvada, Zerit, Ziagen |
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Term
| What are Examples of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)? |
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Definition
| Atripla (he also listed this under Reverse transcriptase inhibitors???), Intelence, Sustiva (vivid dreams), Viramune |
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Term
| What are Examples of Protease Inhibitors? |
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Definition
| Aptivus, Invirase, Lexiva, Prezista, Reyataz, Viracept, Crixivan, Kaletra, Norvir |
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Term
| What are examples of Entry Inhibitors? |
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Definition
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Term
| What is an Example of an Integrase Inhibitor? |
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Definition
| Isentress (interferes with nuclear RNA integration - the virus can't get into the nucleus to make more RNA so it may be effective at reducing reservoir sites) |
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Term
| What is the MEGA-HAART Treatment strategy for HIV? |
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Definition
| Try to get 2-3 categories of agents represented so you don't develop resistance to the drugs; Strategy of combining 6 or more drugs |
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Term
| How Many Mutations of the HIV Virus are Possible Per Day? What are the implications of this? |
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Definition
| 30,000 - given the propensity of the virus to mutate you need to use multiple drugs in different categories to treat patients with HIV so that the virus doesn't develop resistance to the drugs |
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Term
| Within What Time Frame Must HIV Exposure Prophylaxis Be Initiated? |
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Definition
| 72 hours; Treatment should last 4 weeks at a minimum (Dr. Stein offers patients 6-8 weeks), Use of 2 or 3 appropriate medications (sometimes there is decreased compliance with 3 drugs though), Base choices on known pattern of treatment if info is available |
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Term
| Factors that Contribute to Level of Risk of Contracting HIV From Blood |
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Definition
| Percutaneous - 0.3%, Mucous Membrane - 0.09%; Level of risk includes quantity of blood exposure - device visibly contaminated, procedure that involved needle placed directly into artery or vein, deep injury, hollow bore needles, high viral load in source patient, end stage AIDS in source patient |
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Term
| Causes of Death in Patients with HIV |
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Definition
| 1) Hep C, 2) Poor adherence to medications, 3) Failure to diagnose disease until it is advanced, 4)Non-Hodgkin Lymphoma, 5)Non-AIDS cancer, 6)Cardiovascular complicaitons, 7)Care by inexperienced practitioner, 8)Bacterial Infections, 9)Illicit drug use, 10)Treatment toxicity |
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Term
| Main Non-AIDS cancers seen in Patients with HIV |
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Definition
| Lung cancer, Non-Hodgkin's Lymphoma, Liver cancer (assocated with Hep C), Anal and Vaginal Cancer (HPV related), Head and neck cancers |
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Term
| Drugs Used to Treat High Cholesterol in Patients with HIV |
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Definition
| Need to be aggressive in treatment; Lipitor, etc can't be used because they alter the CYP450 system which affects HIV medication metabolism; Use: Welchol, or Pravachol |
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Term
| Metabolic Toxicities Caused by Treatment for HIV |
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Definition
| Lipid Disorders (increased cholesterol, fat deposition disorders), Mitochondrial toxicity (patients can't make muscle), Body Habitus Changes (fat deposition, lack of muscle, etc.), Glucose metabolism (diabetes/ insulin resistance), Bone density |
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Term
| Lipid Abnormalities in Patients Receiving HIV Treatment |
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Definition
| PI recipients are 4.2x more likely to develop a 50 point increase in total cholesterol; Ritonavir>Indinavir>Nelfinavir; Treatment - statins, fibrates; Switching to NNRTIs does lower cholesterol |
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Term
| Fat Maldistribution in Patients Receiving HIV Treatment |
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Definition
| Accumulation - dorsocervical fat, breasts and visceral; Fat Loss - face and extremities (etiology unknown - mitochondrial toxicity??); Management - diet and exercise, anabolic steroids, recombinant human growth factor, switch from PI to Non-PI regimen |
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Term
| Normal PT, Increased PTT, Increased BT, Normal Fibrinogen, Normal D-Dimer |
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Definition
| Characteristic of vWD - the degree of increase in PTT and BT is related to the severity of the disease(I - mild increase, II - large increase) |
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Term
| Normal PT, Increased PTT, Normal BT, Normal Fibrinogen, Normal D-Dimer |
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Definition
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Term
| Increased PT, Normal PTT, Normal BT, Normal Fibrinogen, Normal D-Dimer |
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Definition
| Early Vitamin K Deficiency (affecting only clotting factor 7) |
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Term
| Increased PT, Increased PTT, Normal BT, Normal Fibrinogen, Normal D-Dimer |
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Definition
| Late Vitamin K Deficiency (affecting factors 2,7,9,10) |
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Term
| Increased PT, Normal to Increased PTT, Normal to Increased BT, Normal to Increased Fibrinogen, Normal to Increased D-Dimer |
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Definition
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Term
| Increased PT, Normal to Increased PTT, Increased BT, Normal Fibrinogen, Increased D-Dimer |
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Definition
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Term
| Increased PT, Decreased PTT, Increased BT, Increased Fibrinogen, Increased D-Dimer |
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Definition
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Term
| Increased PT, Increased PTT, Increased BT, Decreased Fibrinogen, Increased D-Dimer |
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Definition
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