Path Exam 2 Review Flashcards
Iron deficiency anemia may be characterized as what type of maturation defect?
Cytoplasmic
What is the functional classification of iron deficiency anemia? morphologic classification?
Iron deficiency is an example of ineffective erythropoiesis. The marrow has increased numbers of erythroid precursors, but they fail to mature appropriately, resulting in decreased production of mature red cells. Iron deficiency is morphologically an example of microcytic hypochromic anemia, along with thalassemia minor and some examples of anemia of chronic disease.
_________ is a special stain that colors hemosiderin (a storage form of iron) blue.
Prussian blue
What is the biochemical basis of delayed nuclear maturation in megaloblastic anemias?
Folate is required for the synthesis of deoxythymidylate monophosphate, which in turn is required for DNA synthesis. Vitamin B12 is essential for the synthesis of the biologically active form of folic acid, tetrahydrofolate. Thus, in vitamin B12 deficiency, there is an internal folate deficiency.
What are other causes of macrocytic anemia?
Other causes of macrocytic (but not megaloblastic) anemia include reticulocytosis, alcoholism, liver disease, dyserythropoietic bone marrow disorders, and hypothyroidism, but the MCV rarely reaches levels above 110 to 115 fL in these disorders. These are not due to impaired DNA synthesis.
Why does the normoblast contain increased mRNA?
The reason the normoblast has increased mRNA is because it is assembling the cellular machinery to engage in protein production: specifically, the hemoglobin alpha and beta globin molecules.
How does one explain the marked hypercellularity of the marrow in megablastic anemia if the cell cycle is slowed down?
While each proliferating cell is progressing through the cell cycle at a considerably slower rate than normal, a much higher proportion of marrow cells are cycling than in normal marrow.
What is the pathogenesis of aplastic anemia? How is it treated?
Aplastic anemia is characterized by anemia, neutropenia, and thrombocytopenia. It results from a primary failure or immunologically mediated suppression of multipotent myeloid stem cells. As a result, there is inadequate production or release of the differentiated cell lines. Some cases follow exposure to chemicals, drugs, or viral infections (particularly hepatitis). Bone marrow transplantation is curative. In cases where transplantation is not possible, immunosuppressive therapy (eg, antithymocyte globulin, steroids, cyclosporine) is implemented.
What are the major categories of intrinsic red blood cell abnormalities?
Hemoglobin disorders, membrane disorders, and enzyme deficiencies.
What laboratory test results may be used to document increased red cell destruction?
Increased serum indirect bilirubin, increased serum lactate dehydrogenase, decreased serum haptoglobin, and increased fecal urobilinogen.
How does one distinguish ß-thalassemia minor from iron deficiency anemia?
Hemoglobin A2 is elevated in §-thalassemia minor (trait) and normal in the other microcytic anemias.
What are the inheritance pattern, red cell defect, mechanism of hemolysis, and treatment in hereditary spherocytosis?
This disease is caused by a genetic defect (most commonly autosomal dominant) in the red cell membrane cytoskeleton. Abnormal red cells get trapped within the cords of the splenic red pulp and are destroyed by macrophages. Transfusions and/or splenectomy are sometimes necessary.
What is the cause of hemolysis in immune hemolysis?
The in vivo agglutination property of these antibodies is not the cause of the hemolysis; rather, their ability to fix complement on the red cell surface at relatively low temperatures results in intravascular hemolysis. In addition, at 37ĄC, IgM antibody is released from the cell surface, leaving a coating of C3b. This is an opsonin, and such opsonized red cells are destroyed by monocyte-macrophages. Thus, there is extravascular hemolysis as well.
What is the molecular consequence of the t(9;22)?
Translocation of the ABL oncogene on chromosome 9 to the BCR gene on chromosome 22.
Do all cases of CML have a Philadelphia chromosome?
No. It is absent in ~5% of cases. However, these cases lacking cytogenetic evidence of a Philadelphia chromosome possess an occult BCR/ABL translocation. Thus, the BCR/ABL rearrangement, rather than the cytogenetically evident translocation, is the necessary genetic event in CML.
What is the prognosis of blast transformation of CML?
Dismal. Once blast phase has occurred, the clinical course is generally one of rapid progression to death. Therapy at this time generally confers little benefit.
What does the existence of a lymphoid blast phase imply about the nature of the transformed cell in CML?
It implies that the pluripotent stem cell that is transformed in CML has the capacity to differentiate into B cells. In fact, patients with CML commonly have circulating mature B cells containing the Philadelphia chromosome.
Is there any clinical significance to distinguishing lymphoid from myeloid blast phase?
The two forms of blast phase are treated differently. Lymphoid blast phase responds better to therapy than does myeloid blast phase, and thus there is a somewhat longer survival (although it is still poor).
What are the main clinical manifestations of P. vera?
Thrombosis and hypertension.
Does P. vera undergo any type of transformation? Is the rate of transformation related to the form of therapy?
Blast phase supervenes in 1-10% of patients. The low end of this range is seen in patients who are treated with phlebotomy, whereas much higher rates of blast phase occur in patients treated with alkylating agents or 32P. A second type of transformation is known as the spent phase. This represents progressive marrow fibrosis with eventual marrow failure and death due to the consequences of cytopenia. This occurs in 10-20% of patients.
What are the clinical manifestations of ET?
Hemorrhage (most commonly) and thrombosis. The paradoxical presence of hemorrhage in a state with increased platelets is due to abnormalities of platelet function in this disorder.
