RBC Disorders

  1. define anemia
    reduction in red cell mass with consequent decrease in oxygen transport capacity of the blood
  2. what are 3 parameters measured to check for anemia
    • 1. red cell count
    • 2. hemoglobin concentration
    • 3. hematocrit
  3. define polycythemia
    increase in red cell mass
  4. list 3 categories of anemia
    • 1. RBC (blood) loss
    • 2. decreased RBC survival
    • 3. decreased RBC production
  5. describe hemolytic anemia
    characterized by shortened red cell survival and retention of products of red cell destruction (iron).
  6. define intravascular hemolysis
    • rbcs are destroyed in circulation. Hb released from RBC bind to haptoglobin and cleared from circulation by the liver. decrease in serum haptoglobin is a key feature of intravascular hemolysis.
    • when Hb levels exceed haptoglobin, free Hb is excreted in the urine (hemoglobinuria).
  7. define extravascular hemolysis
    • destruction of RBCs in the reticuloendothelial system (spleen, liver). examples include hereditary spherocytosis, sickle cell, and erythroblastosis fetalis.
    • Hb breakdown products are increased (hyperbilirubinemia) and jaundice may result. spleen and liver become enlarged. chronic elevated levels of bilirubin can cause gallstones.
  8. what is the difference in pathogenesis between intrinsic and extrinsic hemolysis?
    intrinsic defects are usually inherited while extrinsic defects are usually acquired.
  9. list 4 types of Intrinsic Defects of hemolytic anemias
    • 1. membrane defects
    • 2. abnormal Hb
    • 3. lack of globin chains
    • 4. metabolic defect
  10. describe hemolytic anemia intrinsic membrane defects
    • an autosomal dominant inherited defect in the red cell membrane that results in less deformability of RBC causing them to be sequestered and destroyed in the spleen (extravascular hemolysis). the specific defect is usually a qualitative or quantitative deficiency of spectrin (cytoskeletal protein).
    • Example: hereditary spherocytosis
  11. describe hemolytic anemia intrinsic abnormal Hb
    an autosomal codominant single amino acid substitution inherited disorder in the structure of globin chain that causes Hb to gel upon deoxygenation. under low oxygen conditions, the abnormal Hb polymerizes causing the RBC to form into a sickle shape. the sickled cells are rigid and prone to splenic sequestration (decreased survival) and can also block microcirculation causing ischemia and/or infarction.
  12. describe hemolytic anemia intrinsic lack of globin chain defect
    • inherited autosomal codominant (deletion mutation or mRNA instability) disorder causing diminished or absent synthesis of either the alpha or beta globin chains of Hb.
    • Example: thalassemia (extravascular hemolysis) - reduced globin chain amounts causes decreased Hb. anemia is principal clinical manifestation.
  13. describe hemolytic anemia intrinsic metabolic defect
    x-linked inherited defect causing G6PD deficiency in which red cells are susceptible to oxidant injury by drugs or toxins. denaturation of oxidized Hb causes it to precipitate within the cell and attach to the RBC membrane. RBC membrane flexibility is reduced and causes extravascular hemolysis. this is asymptomatic in absence of oxidant.
  14. describe hemolytic anemia extrinsic immune destruction
    • example: erythroblastosis fetalis.
    • blood group incompatibility between mother and fetus. fetal RBC express antigens inherited from the father that are not present in the mother. the mother's immune system creates antibodies (IgG) that cross the placenta and attach to fetal RBCs resulting in extravascular hemolysis in the fetus.
    • Rh- mothers are giving anti-D within 72 hours of delivering an Rh+ fetus. anti-D binds to the Rh+ fetal RBCs and removes them from maternal circulation before the mother can generate an antibody response and become sensitized.
  15. list 3 examples of immune destruction in terms of extrinsic hemolytic anemia
    • 1. erythroblastosis fetalis
    • 2. hemolytic transfusion reaction - transfusion of incompatible RBCs into a sensitized patient resulting in binding of Ab to RBC Ag causing immediate intravascular hemolysis
    • 3. autoimmune hemolysis
  16. describe mechanical trauma in terms of extrinsic hemolytic anemia
    RBCs are disrupted by physical trauma as they pass through areas of turbulence and abnormal pressure related to abnormal valve function (can be due to a cardiac valve prosthesis). an example is DIC where RBCs are lysed as they pass through fibrin clots/strands in the microcirculation
  17. give an example of an infection causing extrinsic hemolytic anemia
    malaria: parasites infect RBC and cause lysis of RBC during maturation
  18. list 3 causes of nutritional anemias
    • 1. iron deficiency
    • 2. B12 deficiency
    • 3. folate deficiency
  19. describe iron deficiency anemia
    red cells are smaller and contain less Hb than usual. most common cause of anemia worldwide.
  20. describe megaloblasic anemia
    caused by a B12/folate deficiency. both are involved directly or as cofactors for thymidine production. impaired dna synthesis causes a delay in mitotic division causing increased nuclear size but normal RNA synthesis and cytoplasmic maturation. the end result is an abnormally large red cell precursor (megaloblast), decreased production of mature RBCs and abnormally large red cells. the megaloblasts accumulate in the bone marrow, releasing too few RBCs into peripheral blood and causing anemia.
  21. describe aplastic anemia
    • stem cell abnormality resulting in decreased red cell production and all cellular elements of the blood (pancytopenia). usually idopathic but viruses (hepatitis), drugs (chloramphenicol) and toxins (benzene, radiation have been implicated
    • two theories of pathogenesis: acquired defect in stem cell production or suppression of stem cells by T-lymphocytes
  22. describe myelophthisic anemia
    normal elements of marrow are crowded out by a tumor of fibrosis leading to decreased production of red cells.
Card Set
RBC Disorders