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66 Cards in this Set
- Front
- Back
What is the cause of Megaloblastic Anemia?
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Vitamin B12 or Folate deficiency
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Describe why Vitamin B12 and Folate deficiencies cause Megaloblastic Anemia
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Both are needed for DNA synthesis (Thymidine production) - without DNA Synthesis Erythroid precursor cells cannot replicate
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Describe the Absorption of Vitamin B12
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1. B12 is released from its protein-bound form by the action of pepsin and then binds to Salivary Vitamin B12 binding proteins = Cobalophilins or R-binders
2. R-Vitamin B12 complexes are broken down by Pancreatic Proteases in the Duodenum 3. Released B12 then attaches to Intrinsic Factor (from Parietal Cells) 4. IF/B12 attaches to receptor in the Ileum 5. Passed on to Transcobalamin II = plasma transport protein |
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What 3 processes is Vitamin B12 involved in?
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1. Converts 5-methyl-THF to THF
2. converts Homocysteine to Methionine 3. Methylmalonyl CoA --> Succinyl CoA **1&2 involve both B12 and Folate |
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What could be 3 general causes of Vitamin B12 deficiency?
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1. Decreased intake = i.e. vegetarian
2. decreased Absorption 3. Increased requirement |
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What 6 things could cause decreased absorption of Vitamin B12?
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1. Pernicious Anemia = IF deficiency
2. Gastrectomy = IF deficiency 3. Malabsorption (IBD) 4. Ileal resection 5. Bacterial overgrowth 6. Fish Tapeworm --> Diphyllobothrium latum |
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What 3 things could cause an increased need for Vitamin B12 and result in its deficiency?
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1. Pregnancy
2. Hyperthyroidism 3. Cancer |
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What is the function of Folate?
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Involved in 1-carbon transfers in producing Thymidine for DNA synthesis
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What things are associated with decreased intake of Folic Acid?
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Alcoholism and infancy
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What 3 things would cause decreased absorption of Folate?
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1. Malabsorption (Sprue)
2. Drugs = Anticonvulsants, Oral contraceptives 3. Intestinal disease (Lymphoma) |
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What would cause an increased loss of Folate?
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Hemodialysis
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What 4 things would cause an increased requirement for Folate and therefore cause deficiency?
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1. Pregnancy
2. Infancy 3. Cancer 4. increased Hematopoiesis |
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What drug impairs the use of Folate
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-Methotrexate = inhibits DHF Reductase-
-5-FU = inhibits Thymidylate Synthase |
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Describe the pathogenesis of Megaloblastic Anemia
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1. B12 or Folate Deficiency
2. Decreased DNA synthesis 3. Impaired nuclear maturation 4. Megaloblastic anemia |
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Describe how Pernicious Anemia causes Megaloblastic Anemia
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-Autoimmune disease in which Parietal Cells/IF is absent
-Lack of IF results in lack of absorption of Vitamin B12 |
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Pernicious Anemia Antibody mechanism of action
-I -II -III |
I = block B12 binding to IF
II = block B12/IF binding to Ileal receptor III = against gastric proton pump |
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What features can be seen on Blood Smear in Megaloblastic Anemia? (2)
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1. Macro-ovalocytes = ↑ MCV
2. Hypersegmented Neutrophils -have 7-10 lobes instead of 2-4 |
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What Lab findings are consistent with Megaloblastic Anemia due to B12 deficiency? (3)
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1. decreased SERUM B12
2. Increased Methylmalonic Acid 3. Increased serum Homocysteine |
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What lab finding is consistent with Megaloblastic Anemia due to Folate Deficiency?
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Decreased *Red Cell* Folate
**Serum is not measured |
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Compare the length of time it takes to become deficient in B12 vs. Folate
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B12 deficiency takes years to become deficient because it is stored in the LIVER
Folate deficiency can arise within months |
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Do Neurological problems occur in patients with B12 or Folate deficiency?
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B12
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What are the 3 clinical features of B12 deficiency?
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1. Megaloblastic anemia
2. Atrophic Glossitis = red & enlarged tongue 3. Neurologic abnormalities = ataxia, impaired proprioception and vibratory sensation |
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Type of anemia associated with Iron Deficiency?
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Hypochromic Microcytic anemia
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Which is absorbed more readily, Heme Iron or Non-heme iron?
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Heme iron
**25% of Heme iron vs. 1-2% of non-heme iron is absorbable |
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What is the physiological storage form of Iron?
What is the transport protein for Iron? Degraded Ferritin + Lysosomal debris = ? |
Ferritin
Transferrin Hemosiderin |
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What is the most important function of Transferrin?
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to deliver Iron to cells, including Erythroid precursors, which require iron for Hemoglobin synthesis
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What is the daily requirement of Iron?
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1 mg absorbed or 10-20mg dietary
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Globally, what is the most important cause of Iron deficiency?
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Decreased Dietary Intake
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In the US, what is the most important cause of Iron Deficiency?
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Chronic blood loss
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What would be possible causes of Chronic blood loss and Iron deficiency?
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1. GI = peptic ulcers, hemorrhagic gastritis, gastric CA, Colon CA,)
2. GYN = menorrhagia, uterine cancer 3. GU = renal, pelvic, or bladder tumors |
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What are the abnormal Lab values in Iron Deficiency Anemia?
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Decreased
-Serum Iron -Serum Ferritin -Transferrin saturation Increased -Total Iron Binding capacity (TIBC) -Transferrin receptor -Free Erythrocyte Protoporphyrin |
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What are the Blood Smear findings of Iron Deficiency Anemia?
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1. Hypochromic microcytic anemia
2. Decreased MEAN CELL VOLUME (MCV) |
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What are the clinical features of Iron Deficiency Anemia
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1. Hypochromic, microcytic anemia
2. Atrophic glossitis 3. Koilonychia = spoon nails with abnormal splitting 4. Plummer-Vinson Syndrome = Esophageal Webs, Glossitis, Iron Deficiency |
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What is Plummer-Vinson Syndrome?
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1. Esophageal Webs
2. Glossitis 3. Iron Deficiency **increased risk for developing Esophageal Cancer |
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What is the treatment for Iron Deficiency?
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1. Iron supplementation
2. Investigation and treatment of the underlying disease |
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Describe the pathogenesis of Anemia of Chronic Disease
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-
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Most common cause of anemia among hospitalized patients in the U.S.
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Anemia of Chronic Disease
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What are the possible underlying disease causing Anemia of Chronic Disease?
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1. Chronic microbial infections
2. Chronic Immune Disorders = Rheumatoid arthritis 3. Neoplasms = Hodgkin's and Lung/Breast CAs |
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How do cytokines and inflammatory modulators cause anemia of chronic disease?
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Lead to decreased Renal EPO secretion
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What are the 2 ways in which anemia is caused in chronic disease?
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1. Cytokines cause decreased renal EPO secretion
2. Impaired Iron Utilization -> IL-1 causes increased Lactoferrin, which in turn traps iron in BM macrophages **Lactoferrin is an antimicrobial protein that has a high affinity for Iron |
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What are the lab findings in Anemia of Chronic Disease?
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1. Low serum Iron
2. Low Total Iron Binding Capacity (TIBC) 3. High Serum Ferritin *normal serum transferrin receptor |
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How do you differentiate between Iron deficiency anemia and Anemia of Chronic Disease?
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Iron deficiency = low serum ferritin and high TIBC
Anemia of Chronic Disease = high serum ferritin and low TIBC |
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What is the treatment for Anemia of Chronic Disease?
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1. treatment of underlying disorder
2. Recombinant EPO |
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Define Aplastic Anemia
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Hypocellular Bone Marrow with almost total loss of hematopoietic cells, including Erythroid and Myeloid precursor cells
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What are 65% of the causes of Aplastic Anemia?
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Idiopathic
-Stem Cell defect OR -autoimmune dysfunction of cytotoxic T cells |
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What chemicals can cause Aplastic Anemia?
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1. Alkylating agents
2. Benzene 3. Chloramphenicol 4. Insecticides 5. Antimetabolites (5-FU, Methotrexate 6. Arsenicals |
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What viral infections can typically cause Aplastic Anemia?
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1. Parvovirus B19
2. EBV 3. CMV 4. HIV 5. Herpes VZV 6. HCV |
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T or F: Radiation can cause Aplastic Anemia
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True
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In about 50% of cases, what response removes Hematopoietic cells from the BM and causes Aplastic Anemia?
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T-cell response
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What is the inherited form of Aplastic Anemia?
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Fanconi anemia
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What are the lab findings of Aplastic Anemia?
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1. Anemia = fatigue
2. Neutropenia = recurrent infections 3. Thrombocytopenia = bleeding and petechiae |
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Describe the pathogenesis of Aplastic Anemia
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-
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Hypocellular Bone Marrow in Aplastic Anemia
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What is this showing?
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What is the treatment for Aplastic Anemia (2)
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1. Immunosuppression -> Antithymocyte globulin
2. Bone Marrow Transplantation |
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What is Pure Red Cell Aplasia associated with?
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Thymoma = tumor of the thymus
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What is Myelophthisic Anemia?
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Anemia caused by Bone Marrow replacement, most often by a malignant neoplasm
**can also be due to Marrow Fibrosis |
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How could Chronic Renal Failure lead to anemia?
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decreased synthesis of EPO
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What is Polycythemia?
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increased concentration of RBC's, usually with a corresponding increase in Hb levels
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What is the cause of Relative Polycythemia?
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Any kind of dehydration that causes increased concentration of RBC's
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What is Absolute Polycythemia?
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An actual increase in the # of RED CELL MASS
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What is Primary Absolute Polycythemia?
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Caused by an intrinsic abnormality of Myeloid Stem Cells
-clonal proliferation (polycythemia vera) -increased responsiveness to EPO due to mutation in the EPO receptor |
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What is Secondary Absolute Polycythemia?
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Presents with normal Red Cell Progenitors but an increased amount of EPO, which causes proliferation of Erythrocytes
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What are some Appropriate causes of Secondary Absolute Polycythemia?
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1. Lung disease
2. Cyanotic heart disease 3. High altitude |
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What are some Inappropriate causes of Secondary Absolute Polycythemia?
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EPO-secreting tumors
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Megaloblastic Anemia
Macro-ovalocytes and Hypersegmented Neutrophils B12 or Folate deficiency |
What is this picture showing?
How do you know? What is the cause? |
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1. Iron deficiency
2. Hypochromic microcytic anemia (low MCV) 3. Thalassemias = low Hb / Anemia of Chronic Disease = iron is trapped in BM macrophages |
1. What deficiency is this due to?
2. What type of anemia is it? 3. What other 2 diseases could cause it? |