Toxicology Exam 3

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Rx2013
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78838
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Toxicology Exam 3
Updated:
2011-04-11 11:15:08
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Blood Toxicology
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Blood Toxicology
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  1. Study of adverse effects on blood and blood forming tissues
    hematoxicology4
  2. Production of blood cells
    hematopoiesis
  3. Totipotent stem cells
    • can be transformed into any cell
    • embryonic stem cell
  4. Pluripotent stem cell
    • can be transformed into multiple types of cells but not all types
    • ex. bone marrow
  5. Xenobiotics
    compounds that are non-native to the body
  6. Anemia
    • decreased RBC production
    • increased RBC destruction
  7. Erythrocytosis
    increased RBC count
  8. Adult Hemoglobin structure
    • MW = 68Kd
    • 2 alpha and 2 beta globin chains, each with heme
  9. alpha hemoglobin chain has ____ amino acids while beta chain has ____ amino acids.
    • 141
    • 146
  10. Methemoglobin reductase reactivates hemoglobin by
    reducing the iron center from Fe3+(ferric) to Fe2+(ferrous) (active state).
  11. Normal concentrations of hemoglobin
    • men: 13.5-16.5 g/dl
    • women: 12.1-15.1 g/dl
    • children: 11-16 g/dl
    • pregnancy: 11-12 g/dl
  12. fetal hemoglobin consists of
    2 alpha and 2 gamma chains
  13. Adult hemoglobin A
    • 95% of hemoglobin in the body
    • 2 alpha and 2 beta chains
  14. Adult hemoglobin A2
    • 1.5-3.5% of hemoglobin in the body
    • 2 alpha and 2 delta chains
  15. hemoglobin F
    • rare
    • fetal hemoglobin
    • 2 alpha chains and 2 gamma chains
  16. Hemoglobin H
    • seen in alpha thalassemia
    • 4 beta chains
  17. Hemoglobin S
    • seen in sickel cell anemia
    • 2 alpha chains and 2 beta-S chains
  18. Hemoglobin C
    • mild chronic hemolytic anemia
    • 2 alpha chains and 2 beta C chains
  19. Heme and hemoglobin synthesis
    • In Mitochondria: glycine + succinyl-CoA
    • In Cytoplasm: coproporphyrinogen III
    • Back to mitochondria: + Fe2+ => Heme
    • Back to cytoplasm: +Globin => hemoglobin
  20. Sideroblastic Anemia
    • any situation that inhibits heme synthesis
    • can be caused by ethanol, chloramphenicol, isoniazid, copper chelation, pyrazinamide, zinc and lead
  21. Megaloblastic anemia
    • distruction of RBCs
    • normal life span is 120 days
    • Vitamin B12 deficiency
    • Folate deficiency
  22. Vitamin B12 deficiency can result from
    • colchicine
    • neomycin
    • ethanol
    • zidovudine
    • omeprazole
  23. Folate deficiency can result from
    • phenytoin
    • promidone
    • carbamazepine
    • phenobarbitol
  24. Aplastic anemia characterized by
    • peripheral blood pancytopenia
    • reticulocytopenia
    • bone marrow hypoplasia
  25. Aplastic anemia may be caused by
    chloramphenicol, gold, PCN/methycillin, mefloquine, indomethacin, mepazin, bismuth, streptomycin, sulfonamides, mercury, allopurinol, benezne, amphotericin B, pyrimithime
  26. Methemoglobin
    • iron in Fe3+ state (ferric)
    • we can survive with up to 10% of methemoglobin
    • decreased oxygen binding affinity
  27. 3 major extinsic factors that influence oxygen binding affinity of heme
    • pH (direct correlation)
    • 2,3-biphosphoglycerate (increases efficiency)
    • temperature (inverse correlation)
  28. Non-immune hemolytic anemia
    • microangiopathic anemia
    • infectios diseases
    • oxidative hemolysis
    • nonoxidative chemical induced hemolysis
  29. Microangiopathic anemia
    • fragmented RBCs in blood
    • caused by doxorubicin or hemangiosarcoma in dog
  30. Infectios diseases resulting in non-immune hemolytic anemia
    • malaria
    • babesiosis
  31. Oxidative hemolysis results from
    • too many oxidative free radicles that destroy RBCs
    • acetanalide, napthalene, phenylhydrazine, nitrobenzene, methylene blue
  32. Non-oxidative chemical induced hemolysis results from
    • arsine
    • lead
  33. Immune hemolytic anemia causes
    • penicillin: binds to hapten = RBC lysis
    • quinidine: binds RBC = conformation change
    • alpha-mehtyldopa: autoantibody = RBC destruction
  34. Agranular leukocytes
    • lymphocytes
    • monocytes
  35. Granular leukocytes
    • basophils
    • neutrophils
    • eosinophils
  36. Drugs that effect granulocyte function
    • methotrexate
    • cytosine
    • arbinoside
    • daunorubicin
    • cisplatin
    • cyclophosphamide
    • nitrosureas
  37. Drugs that effect granulocyte function
    • ethanol & glucocorticoids: inhibit phagocytosis
    • Iohexol and loxaglate: inhibit superoxide production
    • zinc, heroin and methadone: inhibit chemotaxis
  38. Acute leukemia
    • acute lymphoblastic leukemia (ALL)
    • acute myelogenous leukemia (AML)
  39. Chronic leukemia
    • chronic lymphocytic leukemia (CLL)
    • Chronic myelogenous leukemia (CML)
    • myelodisplastic syndromes (mds)
  40. Agents that may cause leukemia
    • alkylating agnets (MDS, AML)
    • benzene
    • topoisomerase-II inhibitors, etoposide & teniposide (AML)
    • High dose gamma or x ray irradiation (ALL, AML, CML)
  41. important for haemostatic plug after vascular injury
    platelets
  42. decreased production or increased destruction of platelets
    thrombocytopenia
  43. mechanism of thrombocytopenia
    • penicillin-hapten antibody
    • changes in protein conformation
    • change in conformation of coagulation factors
  44. Thrombocytopenia agents
    • PLA2/COX inhibitors (NSAIDS)
    • interference with agonist and receptor (antibiotics, ticlodipine)
    • calcium channel blockers
  45. Heparin binds factor ___
    4
  46. factors that are dependant on vitamin K for synthesis
    • 2
    • 7
    • 9
    • 10
  47. Conditions associated with abnormal synthesis of vitamin k dependant coagulation factors
    • warfarin
    • rodenticides
    • broad spectrum antibiotics
    • dietary deficiency
    • cholestyramine resin
    • malabsorption syndromes
  48. Xenobiotics that influence factor 5
    • streptomycin/gentamicin
    • PCN/cephalosporins
    • topical bovine thrombin
  49. Xenobiotics that can interfere with factor 8
    • PCN/ampicillin/chloramphenicol
    • phenytoin
    • methyldopa
    • nitrofurazone
    • phenylbutazone
    • isoniazid
    • procainamide
    • practolol
  50. common side effects with warfarin
    • bleeding
    • loss of bone density
    • skin necrosis
    • congenital abnormalities in fetus
  51. common side effects with heparin
    • heparin induced thrombocytopenia
    • elevation of aminotransferase levels
    • hyperkalemia
    • rare: alopecia & osteoporosis

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