Pathophys 3.1

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Rx2013
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36736
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Pathophys 3.1
Updated:
2010-09-22 21:32:19
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Hematology Disorders Red Blood Cells Platelets
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Hematology: Disorders of Red Blood Cells & Platelets
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  1. Development of a RBC
    • Pleuripotent stem cell stimulated by EPO => committed erythroid precursor
    • Maturation of Erythroblast
    • Nucleus extruded
    • Reticulocytes released into blood stream ~ 7 days
    • Reticulocytes converted to RBC ~ 24-48 hours
  2. Diseases that occur due to dysfunction of RBC production
    • Anemia
    • Mutations of hemoglobin
  3. Anemia
    • abnormally low level of circulating RBCs or RBCs with diminished level of hemoglobin
    • Women < 12g/dL
    • Men < 13 g/dL
  4. Causes of Anemia
    • Excessive blood loss
    • over destruction of RBC in periphery or spleen
    • Deficient RBC production
  5. Manifestations of Anemia
    • Decreased presence of hemoglobin in the blood - Pallor
    • Tissue hypoxia due to deficient oxygen transport
    • Recruitment of compensatory mechanisms
  6. Effects of tissue hypoxia
    • weakness
    • fatigue
    • angina
    • - small microvasculature in heart very sensitive to changes in O2
    • - sends signal to brain that there is "pain"
    • headache
  7. Compensatory mechanisms for Anemia
    • tachycardia
    • palpitations
    • dyspnea
    • bone pain (also a side effect of EPO)
  8. Blood loss anemia
    • Rapid blood loss = hypovolemic shock
    • Slow blood loss = may have no symptoms
    • - GI Bleed
  9. Hemolytic Anemia
    • Premature destruction of RBCs
    • Increased iron in blood due to destruction of RBCs
    • Intrinsic = hereditary = fatal
    • Extrinsic = medications, infection, blood clots
    • -RBC reaches site and is destroyed
  10. Sickle Cell Disease
    • Inherited disorder resulting in abnormal hemoglobin and hemolysis; 2 genes
    • Point mutation in beta-chain of the hemoglobin molecule
    • Protective against malaria
    • Poor O2 carrying capacity
  11. Clinical course of sickle cell
    • Hemolytic anemia
    • Chronic hyperbilirubinemia
    • Vaso-occlusive disease/crisis
  12. Presenting symptoms of hemolitic anemia associated with sickle cell disease
    fatigue, pallor, angina, palpitations
  13. Presenting symptoms of chronic hyperbilirubinemia associated with sickle cell disease
    • gallstones
    • jaundice
  14. Presenting symptoms of vaso-occlusive disease/crisis associate with sickle cell disease
    • Pain
    • Kidney disease
    • infarct
    • eye disease
    • splenic enlargement/injury
  15. B-Thalassemia
    • Defect in B-chain synthesis
    • More comon in mediterranean countries
    • Damaged RBC membranes
    • Increased destruction in the spleen
    • Coagulation abnormalities => increased risk for thrombosis
  16. Clinical Manifestation of B-Thalessemia minor
    • sufficient normal Hgb synthesis
    • only a problem in crisis
  17. Clinical Manifestations of B-Thalassemia Major
    • Severe transfusion dependant anemia
    • mpaired bone growth
    • splenic enlargement
    • blood transfusion is the only treatment
  18. Alpha - Thalassemia
    • Defect in the alpha chain synthesis
    • 1 gene deletion; asymptomatic
    • 2 gene deletion; mild hemolytic anemia
    • 3 gene deletion; alpha chain aggregates, moderate hemolytic anemia
    • 4 gene deletion; death
  19. G6PD Deficiency
    • NADP not converted to NADPH in RBC
    • NADPH protects cells from oxidative damage
    • Oxidation converts hemoglobin to methemoglobin which inhibits O2 carrying capacity
  20. Causes of Iron Deficiency Anemia
    • Dietery deficiency
    • Poor absorption (acholoric state)
    • Pregnancy
    • Gastrointestinal loss (bleed)
    • Menstruation
  21. Clinical manifestations of Iron-Deficiency Anemia
    • Low hemoglobin / hematocrit
    • Decreased iron stores
    • low serum iron and ferritin(carries iron)
    • fatigue, pallor, palpitations
    • deformity of fingernails
    • pica
  22. Megaloblastic Anemias
    • Enlarged immature RBCs
    • Slow-developing
    • Usually related to age or medication use
    • B12 deficiency
    • Folic Acid deficiency
  23. Manifestations of B12 deficiency megaloblastic anemia
    • Often asymptomatic
    • Neurologic disease
    • Glossitis
  24. Manifestations of Folate Deficiency Megaloblasic Anemia
    Irritability
  25. Aplastic Anemia
    • Complete bone marrow stem cell reduction or suppression
    • High-dose radiation
    • Chemotherapy
    • Chloramphenicol
    • Complications of severe illness
  26. Manifestations of Aplastic Anemia
    • Weakness, fatigue, pallor
    • petechiae
    • unexplained bleeding or ecchymoses
  27. Anemia of Chronic Disease
    • common in patients with kidney disease
    • inadequate production of epo or body not responding to epo
    • chronic infection
  28. Five Stages of Hemostasis
    • Vessel spasm
    • formation of the platelet plug
    • blood coagulation
    • blot retraction
    • clot dissolution
  29. Hypercoagulability
    • exaggerated form of hemostasis
    • increased platelt function or accelerated activity of the clotting system
    • Risk for DVT and PE
  30. Thrombocytosis
    • Increased platelets
    • Chronic or Reactive
  31. Reactive Secondary Thromocytosis
    • increased platelets in response to stimuli
    • tumor, infection, trauma...
    • overproduction of inflammatory cytokines
    • common in hospitalized patients
  32. Inherited increased clotting activity
    • mutations in factor 5 or prothrombin gene
    • antiphospholipid syndrome
    • increased risk for thromboembolic event
  33. Acquired increased clotting activity risk factors
    • venous stasis
    • MI
    • Oral contraceptives
    • Smoking
    • Obesity
    • Cancer &pregnancy
  34. Bleeding disorders
    • impairment of blood coagulation
    • thrombocytopenia
    • decreased coagulation factors
    • decreased vessel integrity
    • spontaneous bleeding
    • aquired disorders more common
  35. Immune Thrombocytopenic Purpura
    • Acute and chronic
    • autoantibodies to platelets
    • complex trapped in spleen and removed
    • antibodies directed at platelets
    • treatment aimed at reducing immune activity
  36. Drug - Induced Thrombocytopenia
    • Drug-induced antibodies to platelets
    • Complex trapped in spleen and removed
    • uniqe reaction with heparin inducing hypercoaguable state
    • treatment aimed at removing offending agent
  37. Thromotic Thrombocytopenia Purpura
    • Rare, Aquired disorder
    • increased recruitment of platelet aggregating substances
    • hemolytic anemia, renal failure, fever and neurologic problems
  38. Von willebrand disease
    • most frequent inherited bleeding disorder
    • DDAVP is the drug of choice
    • inability to stabilize hemostatic plug or anchor clot
  39. Hemophilia
    • lack of factor 8 hemophilia a
    • lack of factor 9 hemophelia b
    • typically expressed in males
    • effects early clotting cascade
  40. Bleeding of hemophilia
    • joint bleeding
    • muscle bleeding
    • chronic pain
    • muscle atrophy

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