Scholar rx qs week 2.pdf

REVIEW QUESTIONS Hereditary Spherocytosis 1. A 24-year-old male presents with a history of fatigue, intermittent yellow skin, and left upper quadrant pain. Physical examination reveals jaundice and splenomegaly. The patient notes that his father was...

REVIEW QUESTIONS Hereditary Spherocytosis 1. A 24-year-old male presents with a history of fatigue, intermittent yellow skin, and left upper quadrant pain. Physical examination reveals jaundice and splenomegaly. The patient notes that his father was diagnosed with a type of hemolytic anemia. A peripheral smear reveals spherocytes. An EMA (eosin-5-maleimide) binding test is positive. Which of the following is the most likely cause of this patient’s condition? Autoimmune destruction of RBCs Defect in CD55 and CD59 Defect in glucose 6-phosphate dehydrogenase Defect in spectrin Defect in the β-chain of hemoglobin Explanation The correct answer is a defect in spectrin (D). Hereditary spherocytosis (HS) is an inherited disorder of red blood cells (RBCs) resulting from mutations in RBC membrane proteins. Mutations in proteins such as spectrin and ankyrin make the membrane cytoskeleton unstable, and RBCs are more prone to undergo hemolysis. Autoimmune destruction of RBCs (A) may result in spherocytes on a peripheral smear, but splenomegaly makes HS a more likely diagnosis. A defect in CD55 and CD59 (B) is seen in paroxysmal nocturnal hemoglobinuria. A defect in glucose 6-phosphate dehydrogenase (C) is seen in G6PD deficiency. A defect in the β- chain of hemoglobin (E) is seen in sickle cell disease. Spherocytes are not seen in defect in CD55 and CD 59, defect in G6PD, or defect in the β-chain of hemoglobin. 2. Which of the following characteristic laboratory values is most typical of patients with hereditary spherocytosis (HS)? Decreased serum LDH Increased (direct) conjugated bilirubin Increased MCHC Increased MCV Normal RDW Explanation The correct answer is increased MCHC (C). Hereditary spherocytosis (HS) results in a loss of red blood cell membrane and the smaller red blood cells (RBCs) have an increased concentration of hemoglobin (increased mean corpuscular hemoglobin concentration [MCHC]). Because of hemolysis, there would be increased serum lactate dehydrogenase (LDH), an enzyme that leads out of RBCs, not decreased serum lactate dehydrogenase LDH (A). The bilirubin would also be increased in the setting of hemolysis. But normally it would not be increased (direct) conjugated bilirubin (B); it would typically be unconjugated, since it is not yet metabolized by the liver. Increased MCV (D) (mean corpuscular volume) is incorrect; the RBCs do not become larger in HS, which is a normocytic anemia. In HS the hemolysis causes some cells to become smaller and others to remain larger, so there is an increased red blood cell distribution width (RDW), not a normal RDW (E). 3. Which of the following tests would most likely be abnormal in a patient with hereditary spherocytosis (HS), but would be normal in a patient with anemia of chronic disease (ACD)? Blood hemoglobin MCV Osmotic fragility test Serum folate Serum iron Explanation The correct answer is an osmotic fragility test (C). In Hereditary spherocytosis (HS) and any type of spherocytosis, the red blood cells do not have excess membrane and are unable to accommodate excess water. This in turn renders them susceptible to osmotic lysis. Anemia of chronic disease (ACD) does not cause spherocytosis. The blood hemoglobin (A) is low in both. The MCV (B) (mean corpuscular volume) is normal in both conditions. The serum folate (D) and serum iron (E) are usually normal in both conditions. Autoimmune Hemolytic Anemias 1. A patient presents with fatigue and jaundice 1 week after taking a cephalosporin antibiotic for a respiratory infection. A complete blood count (CBC) reveals low hemoglobin and a normal mean corpuscular volume (MCV). A peripheral blood smear shows spherocytes. If positive, which of the following tests would best diagnose autoimmune hemolytic anemia in this patient? Low blood hemoglobin Normal mean corpuscular volume Positive direct antiglobulin test Presence of jaundice Spherocytosis on the blood smear Explanation The correct answer is positive direct antiglobulin test (C). Autoimmune hemolytic anemias can be differentiated from nonimmune hemolytic anemias using the direct antiglobulin test (DAT). It is positive in autoimmune hemolytic anemia but negative in other, nonimmune hemolytic anemias. The remaining distractors are not specific for autoimmune hemolytic anemia. All anemias have a low blood hemoglobin (A), and there are lots of anemias (many of them hemolytic) with a normal mean corpuscular volume (B). Presence of jaundice (D) can be seen in any hemolytic anemia. Spherocytosis on the blood smear (E) is seen in other conditions such as hereditary spherocytosis and systemic infections. 2. A patient was recently diagnosed with cold autoimmune hemolytic anemia. In addition to advising the patient to avoid cold temperatures, which of the following treatments is most appropriate, if symptoms become severe? Blood (RBC) transfusion Hydrocortisone Prednisone Rituximab Splenectomy Explanation The correct answer is rituximab (D). Rituximab is an anti-CD20 medication. CD20 is located on B cells, so this B-cell antagonist can help prevent the release of the antibodies. Rituximab is a potential treatment for both warm and cold autoimmune hemolytic anemia (AHA). Since AHA is defined by circulating autoantibodies, performing a blood (RBC) transfusion (A) is not particularly useful, since the newly transfused red blood cells may also be coated by the autoantibodies. In addition, glucocorticoids like hydrocortisone (B) and prednisone (C) have not been found to be clinically useful in these patients. Cold AHA is characterized predominately by intravascular hemolysis due to IgM-induced complement activation. Removing the spleen, splenectomy (E), is not useful in these patients. 3. Which of the following laboratory findings would be least likely in a patient with cold autoimmune hemolytic anemia (AHA)? Decreased haptoglobin Decreased mean corpuscular volume Increased reticulocytes Positive DAT RBC agglutination Explanation The correct answer is decreased mean corpuscular volume (B). Autoimmune hemolytic anemia (AHA) is a normocytic anemia, so the mean corpuscular volume is normal. Decreased haptoglobin (A) is found because haptoglobin is used up in an attempt to clear away the free hemoglobin in circulation. Increased reticulocytes (C) are caused by the bone marrow trying to compensate for the loss of red blood cells (RBCs) by releasing immature cells into circulation. A positive DAT (D) is diagnostic of AHA, as it proves the presence of anti-RBC antibodies. RBC agglutination (E) may be seen on the peripheral blood smear of patients with cold AHA. Sickle cell disease  1. Which of the following types of mutations most often causes sickle cell disease? Frameshift mutation Nonsense mutation Point mutation Splicing mutation Trinucleotide repeat Explanation The correct answer is point mutation (C). Sickle cell disease (SCD) is caused by a point mutation in the β-globin chain gene. The mutation is not a frameshift mutation (A) or nonsense mutation (B). Splicing mutations (D) and trinucleotide repeat (E) mutations are present in several diseases, but they are not seen in hemoglobinopathies (including sickle cell disease). 2. Which of the following conditions most promotes red blood cell (RBC) sickling? Acidosis Alkalosis Decreased 2,3-bisphosphoglyceric acid (2,3-BPG) Decreased temperature Fetal hemoglobin Explanation The correct answer is acidosis (A). Acidosis, increased 2,3-bisphosphoglyceric acid (2,3-BPG), fever, and altitude all shift the hemoglobin dissociation curve to the right, favoring a deoxygenated state that would promote sickling in sickle cell disease (SCD). Alkalosis (B), decreased 2,3- bisphosphoglyceric acid (2,3-BPG) (C), decreased temperature (D), and fetal hemoglobin (E) all cause a shift of the curve to the left, which would decrease sickling. 3. A 27-year-old male presents to the emergency department with shortness of breath, mild fever, and chest pain that he rates as 10/10 intensity. There is no cough. His oxygen saturation is 88%. A review of his chart shows one to two admissions per year due to infection and/or bone pain. The blood smear shows sickled red blood cells (RBCs). The chest x-ray is normal. Which of the following treatments would most quickly correct the patient’s low oxygen saturation? Antibiotics Exchange transfusion Folate Hydroxyurea Ibuprofen Explanation The correct answer is exchange transfusion (B). Based on the patient history and presenting symptoms, the patient most likely has sickle cell disease (SCD) and is experiencing acute chest syndrome, marked by chest pain, fever, shortness of breath, and hypoxemia. Management should include pain control, fluids, oxygen supplementation, and exchange transfusion. Folate (C) and hydroxyurea (D) have roles in the chronic management of SCD, but not in this acute setting. Ibuprofen (E) and opiates are used to manage pain episodes, but do not correct the hypoxia. Antibiotics (A) are sometimes needed when there is concurrent pneumonia or other infection, but there is no evidence of that here, since the chest x-ray is normal and there is no cough. 4. Which of the following is the most useful to manage the symptoms of an acute pain episode in a patient with sickle cell disease (SCD)? Analgesic drugs Folic acid Hydroxyurea Stem cell transplantation Transfusion with whole blood Explanation The correct answer is analgesic drugs (A). Appropriate pain management is essential during severe vaso-occlusive episodes. Folic acid (B) can be used to improve baseline hemoglobin levels, but it does not act fast enough to be effective in an acute setting. Likewise, hydroxyurea (C) is useful for increasing the number of normal red blood cells (RBCs) in circulation, but it is not particularly helpful during a pain episode. Stem cell transplantation (D) can be considered for patients with severe complications, but it is a long, carefully planned process that requires extensive investigations. While RBC transfusions are often used to treat some sickle cell disease (SCD) complications such as acute chest syndrome, transfusion with whole blood (E) is not used routinely and is reserved for acute bleeding, for example, after trauma. Thalassemias 1. Which of the following genetic defects is present in hemoglobin H disease? Deletion of one β chain gene Deletion of three α chain genes Mutation of all four α chain genes Mutation of both β chain genes Mutation of one α chain gene Explanation The correct answer is deletion of three α chain genes (B). HbH disease is a severe form of α- thalassemia in which three of the four α chain genes are deleted, and the excess β chains form a HbH tetramer. Deletion of one β chain gene (A) is incorrect, as β chain deletions are not present in α- or β-thalassemia (β-thalassemia is characterized by mutations, not deletions, in β chain genes). α-Thalassemias are characterized by deletions of α chain gene, not non- deletional mutations, which makes both mutation of all four α chain genes (C) and mutation of one α chain gene (E) incorrect. Mutation of both β chain genes (D) is present in β-thalassemia intermedia and β-thalassemia major. 2. Which of the following red blood cell indices is most elevated in severe thalassemia? Hemoglobin Mean cell hemoglobin concentration Mean corpuscular volume RBC count RBC distribution width Explanation The correct answer is RBC distribution width (E). The red blood cell distribution width (RDW) is a measure of anisocytosis (variation in red cell size); the higher the RDW, the greater the range of red cell sizes present. In severe thalassemia, the RDW is elevated because although all the red cells are small, their sizes vary. In mild thalassemia the RDW is low to normal. Hemoglobin (A) is decreased in thalassemia, as are the mean cell hemoglobin concentration (B) and mean corpuscular volume (C). The RBC count (D) is increased in milder thalassemias but is decreased in severe thalassemia. 3. Which of the following is the most common complication associated with chronic blood transfusions used to treat severe forms of thalassemia? Graft vs host disease Hepatitis C infection HIV infection Increased hemolysis Iron overload Explanation The correct answer is iron overload (E). Chronic transfusions for any type of anemia (including thalassemia) carry a risk of iron overload unless iron chelators are administered. Graft vs host disease (A) is a potential complication of stem cell transplant but is not seen in normal blood transfusion therapy. Hepatitis C (B) and HIV (C) infections can both be caused by transfusion of infected blood products; however, the risk of contracting hepatitis C or HIV from a transfusion is rare in developed countries because of adequate blood screening. Increased hemolysis (D) is not a risk in patients receiving chronic transfusions, as the risk of being transfused the wrong blood type is very rare. 4. A 25-year-old male presents with easy fatigability and skin discoloration. He is chronically jaundiced and anemic since childhood, requiring transfusions for multiple episodes of severe anemia. Physical exam shows splenomegaly, frontal  bossing, prominent malar eminence and upper teeth, and icterus. The complete blood count (CBC) shows a microcytic, hypochromic anemia. Hemoglobin electrophoresis shows elevated HbA2 and F with undetectable HbA levels. What is the most likely diagnosis in this patient? α-Thalassemia trait β-Thalassemia trait Hemoglobin Bart disease Hemoglobin H disease Transfusion-dependent thalassemia Explanation The correct answer is transfusion-dependent thalassemia (E). This is suggested by the transfusion requirements, anemia, splenomegaly, and bossing (suggesting extramedullary hematopoiesis) with a hemoglobin electrophoresis showing no HbA. α -Thalassemia trait (A) is usually asymptomatic and would show a normal hemoglobin electrophoresis. β-Thalassemia trait (B) is also asymptomatic, and hemoglobin electrophoresis will show low levels of HbA and elevated HbA2 and F. Hemoglobin Bart disease (C) is incompatible with life and causes intrauterine fetal demise. Hemoglobin H disease (D) causes severe symptomatic anemia, however, the levels of HbA, A2, and F will be low while HbH levels will be elevated on electrophoresis. Leukopoiesis 1. At what stage of neutrophil development does specific granulation first appear? Metamyelocyte Myeloblast Myelocyte Promyelocyte Segmented neutrophil Explanation The correct answer is myelocyte (C). Specific (secondary) granules in neutrophils first appear at the myelocyte stage of development. Metamyelocyte (A) does not yet show this differentiation. Myeloblast (B) is the earliest stage in neutrophil development; they don’t have specific granules. Promyelocyte (D) also does not yet show this differentiation. Segmented neutrophil (E) is the most mature stage of neutrophil development; specific granules are present but have appeared first at the earlier myelocyte stage. 2. Which of the following are seen in promonocytes but not monoblasts? Clumpy, smudgy chromatin Cytoplasmic vacuoles Delicate, tissue-paper nuclear folds Granules Large nucleoli Explanation The correct answer is delicate, tissue-paper nuclear folds (C). These nuclear folds are characteristic of promonocytes; they are not seen in the other stages of the monocyte series (or in any stages of other cell lineages). Clumpy, smudgy chromatin (A) is seen in mature lymphocytes. Cytoplasmic vacuoles (B) can be seen in any stage of monocyte development. Granules (D) may be seen in any stage of monocyte development. Large nucleoli (E) are prominent in monoblasts but uncommon in promonocytes. 3. Which of the following cell lineage produces antibody-secreting cells? Erythroblast Lymphoblast Megakaryocyte Monoblast Myeloblast Explanation The correct answer is lymphoblast (B). These cells differentiate into lymphocytes and natural killer (NK) cells. The lymphocytes then may mature in the thymus to form T cells or in the bone marrow to form B cells. When activated, B cells mature to form antibodies. Erythroblast (A) forms red blood cells. Megakaryocyte (C) forms platelets. Monoblast (D) forms monocytes and tissue macrophages. Myeloblast (E) is a precursor cell for granulocytes and monocytes. 4. Which of the following cytokines is more important to eosinophil development than to development of the other granulocytes? IL-2 IL-4 IL-5 IL-12 IL-13 Explanation The correct answer is IL-5 (C). This cytokine causes B cells to release factors that stimulate growth and maturation of eosinophils but is not important in development of other granulocyte types. IL-2 (A) is associated with increase in T cells and NK cells. IL-4 (B) is associated with differentiation of T cells, which signals growth of B cells. IL-12 (D) also is associated with increase in T cells and NK cells. IL-13 (E) is a potent macrophage activator, inducting migration of monocytes to tissues to form macrophages. Benign Leukocytosis 1. A 46-year-old female presents at the clinic with complaints of fever, sweating, and fatigue. The complete blood count (CBC) is notable for a total white blood cell (WBC) count of 18,000/mm3 with 60% neutrophils. The blood smear reveals the presence of occasional bands, metamyelocytes, and promyelocytes, along with many mature segmented neutrophils with dark granules in the cytoplasm. Which of the following is the most likely cause of her symptoms? Acute leukemia Chronic myeloid leukemia Infectious mononucleosis Parasitic infection Staphylococcus infection Explanation The correct answer is Staphylococcus infection (E). This patient has neutrophilia (total neutrophil count increased at 9000/mm3) with a left shift (few immature neutrophil forms), characteristic of a leukemoid reaction due to infection or inflammation. The toxic granulations in the neutrophils are most consistent with an infection, accounting for her fever. Acute leukemia (A) would show numerous circulating blast cells. Chronic myeloid leukemia (B) would show a markedly high white blood cell (WBC) count, usually more than 100,000. Infectious mononucleosis (C) is associated with a proliferation of reactive lymphocytes, not neutrophils. Parasitic infection (D) is typically associated with eosinophilia, not neutrophilia. 2. A left shift is seen on the blood smear of a patient admitted to the hospital. Which of the following cell types is most likely to be present in increased numbers? Basophils Eosinophils Immature neutrophils Monocytes Reactive lymphocytes Explanation The correct answer is immature neutrophils (C). A left shift means that neutrophil precursors are present in the blood (typically, only segmented neutrophils are seen). Basophils (A) are elevated in allergies, myeloproliferative disorders, hypothyroidism, and certain infections (eg, influenza, tuberculosis). Eosinophils (B) are elevated in allergies, drug reactions, asthma, and parasitic worm infections. Monocytes (D) are occasionally elevated when a patient has infective endocarditis, syphilis, tuberculosis, autoimmune disorders, and chronic inflammation. Reactive lymphocytes (E) are seen primarily in viral infections. 3. A patient without symptoms has a routine complete blood count (CBC), which shows a total leukocyte count of 10,000 cells/mm3. The differential count shows 50% neutrophils, 45% lymphocytes, 3% monocytes, 1% eosinophils, and 1% basophils. Which of the following disorders is most consistent with this patient’s lab findings? Immature neutrophilia Mature lymphocytosis Mature neutrophilia Monocytosis Reactive lymphocytosis Explanation The correct answer is mature lymphocytosis (B). This patient has a normal total leukocyte count of 10,000/mm3, but an elevated percentage of lymphocytes, leading to a total lymphocyte count of 4500 (normal is under 4000). The total counts of neutrophils are normal (ie,