INTEGRATED BASIC SCIENCES PreTest® Self-Assessment and Review pot

Case Study VSICKLE CELL ANEMIA Integrated Basic Science Content Review Examination of his peripheral blood reveals abnormal-shaped rocytes and occasional Howell-Jolly bodies.. A CBC reve

BASIC SCIENCES

Self-Assessment and Review

Medicine is an ever-changing science As new research and clinical experience broaden our knowledge, changes

in treatment and drug therapy are required The editor and the publisher of this work have checked with sources believed to be reliable in their efforts to provide informa- tion that is complete and generally in accord with the standards accepted at the time of publication However,

in view of the possibility of human error or changes in medical sciences, neither the editor nor the publisher nor any other party who has been involved in the preparation

or publication of this work warrants that the information contained herein is in every respect accurate or com- plete, and they are not responsible for any errors or omissions or for the results obtained from use of such in- formation Readers are encouraged to confirm the infor- mation contained herein with other sources For example and in particular, readers are advised to check the prod- uct information sheet included in the package of each drug they plan to administer to be certain that the infor- mation contained in this book is accurate and that changes have not been made in the reccommended dose

or in the contraindications for administration This ommendation is particular importance in connection with new or infrequently used drugs.

rec-INTEGRATED BASIC SCIENCES

Self-Assessment and Review

EDITOR Earl J Brown, MD

Associate Professor Department of Pathology East Tennessee State University Johnson City, Tennessee

McGRAW-HILL Health Professions Division

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One of the current trends in medical education is to integrate material tween the basic science courses of the first two years of medical schooland to integrate material between the basic science courses and the clini-cal departments Medical students often feel submerged by the flood ofinformation during medical school and attempts to integrate this materialare often met with much frustration The basic premise for this book is tohelp in the integration of material between the basic science courses ofmedical school The questions in this book are grouped in sets of threequestions around a clinical scenario The organization of each of thesethree question sets is as follows: the first question in each group coversanatomy illustrated by the clinical scenario [either gross anatomy, micro-scopic anatomy (histology), or developmental anatomy (embryology)];the second question in each group covers the normal functioning that is il-lustrated by the clinical scenario (either biochemistry, physiology, or im-munology), and the third question of each set covers the abnormal func-tions involving the clinical case (namely pathology, pharmacology, ormicrobiology)

be-The questions in each PreTest® Self-Assessment and Review book lel the format and degree of difficulty of the questions found in the UnitedStates Medical Licensing Examinations (USMLE) Each question is ac-companied by an answer, a paragraph explanation, and a specific pagereference to an appropriate textbook or journal article A bibliographylisting sources can be found following the last chapter of this text An ef-fective way to use this PreTest® is to read a clinical scenario and answerthe set of three questions that are associated with that clinical case Youshould allow yourself about one minute to answer each question in theset As you proceed, indicate your answer beside each question By fol-lowing this suggestion, you approximate the time limits imposed by theStep After you finish going through the questions in each set, spend asmuch time as you need verifying your answers and carefully reading theexplanations provided Pay special attention to the explanations for thequestions you answered incorrectly — but read every explanation The au-thors of this material have designed the explanations to reinforce and sup-plement the information tested by the questions If you feel you need

paral-vii

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further information about the material covered, consult and study the erences indicated This book is directed primarily toward medical stu-dents, especially second year medical students as they prepare for theUSMLE Step 1 Since the book will integrate material from many of thebasic science medical courses, it will also benefit first and second yearmedical students as they study for individual courses during the first twoyears of medical school It will especially be beneficial if they use it to in-tegrate these courses Additionally, since the questions will all be based

ref-on patient histories, this book will also be beneficial to students duringtheir third and fourth years to review basic science course material and in-tegrate this into their clinical experience It will also be beneficial forthese students as they study for the USMLE Step 2

Earl Brown, MD

I would like to express my appreciation and gratitude to my colleagues inthe Department of Pathology for their support and help over the pastdecade that I have been director of the sophomore pathology course at theQuillen College of Medicine I would like to especially thank Dr Philip

S Coogan, the chairman of our department, who has supported my effortsover the years and has enabled me to progress as a teacher I would espe-cially like to express my deep felt thanks to all the many students whoover the years have inspired me with their spirit, their common sense, andtheir enthusiasm They have showed me time and time again different andbetter ways to explain concepts and integrate basic science material Theyhave taught me much Finally, I would like to thank my family, my wifeJanet and my two children Kevin and Heather, who have supported methrough many late-night and weekend typing sessions

ix

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I megaloblastic anemia

II iron-deficiency anemia

III hereditary spherocytosis

IV methemoglobin

V sickle cell anemia

VI porphyria (PCT)

VII aplastic anemia

VIII chronic myeloid leukemia

IX acute myeloid leukemia

X acute lymphoid leukemia

XI severe combined immune deficiency syndrome

XII multiple myeloma

XIII infectious mononucleosis

XIV lymphoma (B cell)

XV immune thrombocytopenia purpura

Physical examination reveals a slightly enlarged spleen and a smooth,beefy-red tongue Neurologic examination reveals a decreased sense

of vibration and position in both her arms and legs The completeblood count (CBC) reveals decreased numbers of erythrocytes, leuko-cytes, and platelets (pancytopenia) along with an increase in the meancell volume (MCV) of the erythrocytes Examination of the peripheralsmear reveals numerous enlarged, oval-shaped erythrocytes (macro-ovalocytes), and many of the neutrophils have more than five lobes(hypersegmented neutrophils) Histologic examination of a smearmade from a bone marrow aspiration reveals asynchrony in red bloodcell (RBC) precursors between the maturation of the nuclei and theircytoplasm Additional workup discovers achlorhydria and chronic at-rophic gastritis

1 Which one of the following sequences correctly describes the normalmaturation sequence of RBC precursors between the proerythroblaststage and bone marrow reticulocytes?

1
basophilic erythroblast

2
orthochromatophilic erythroblast

3
polychromatophilic erythroblast

2

fol-(A) propionyl coenzyme A (CoA) : methylmalonyl CoA

(B) methylmalonyl CoA : succinyl CoA

(C) succinyl CoA 2 : fumarate

(D) malonyl CoA 2 : palmitate

(E) dUMP 2 : dTMP

3 Which of the following tests would most likely indicate the etiology

of this patient’s signs and symptoms?

(A) acid hemolysis test (D) osmotic fragility test

(B) Coombs’ test (E) Schilling test

II A 37-year-old woman presents with fatigue, lethargy, and muscle weakness.

Physical examination reveals pallor of her skin, a smooth tongue, and

a concave shape (“spoon-nails”) of her fingernails Her heart rate isincreased (tachycardia), and her respiratory rate is slightly increased.Examination of her peripheral smear reveals her RBCs to be small andpale (microcytic and hypochromic) and different shapes (poikilocyto-sis) Laboratory evaluation reveals a hemoglobin concentration of10.4 g/dL, and her red cell indexes reveal a mean cell volume of 71

m3and a mean cell hemoglobin (MCH) of 21.5 g/dL Additionaltests reveal the serum iron, serum ferritin, and the transferrin satura-tion to be decreased, but the total iron-binding capacity (TIBC) isincreased

4 Which one of the following statements is INCORRECT concerningthe normal histologic appearance of RBCs in the peripheral blood?

(A) They are anucleate cells as they lack a nucleus.

(B) They are round biconcave disks.

(C) They contain abundant hemoglobin and lack cell organelles.

(D) They contain multiple, finely granular, basophilic cytoplasmic granules (E) They have a central pallor that is about one-third the diameter of the cell.

5 Most of the dietary iron is absorbed in the

(A) stomach

(B) upper part of the small intestines

(C) lower part of the small intestines

(D) upper part of the colon

(E) lower part of the colon

6 Examination of the bone marrow of this individual is most likely toreveal

(A) absent iron stores

(B) iron trapped within macrophages

(C) megaloblastic erythroid maturation

(D) numerous ring sideroblasts

(E) red cell aplasia

Case Study III

7 The spherical erythrocytes (spherocytes) in this individual’s peripheralblood may be the result of an abnormality involving the RBC mem-brane Which one of the following proteins is a peripheral protein ofthe normal RBC membrane?

(A) amyloid (D) protein 3

(B) dystrophin (E) spectrin

(C) fibrillin

8 The abnormal spherical shape of these erythrocytes would most likelyresult in

(A) decreased ability to transport bicarbonate ions

(B) decreased ability to transport chloride ions

(C) increased red cell capacity to expand when placed in a hypotonic salt lution

so-(D) increased red cell lysis when placed in a hypotonic salt solution

(E) resistance to Plasmodium falciparum infection

9 What is the most likely diagnosis for this individual?

(A) hereditary pyropoikilocytosis

(B) hereditary spherocytosis

(C) paroxysmal cold hemoglobinuria

(D) paroxysmal nocturnal hemoglobinuria

(E) pyruvate kinase deficiency

Cause of Abnormality (Brown Color)

IV A 5-year-old boy is being evaluated for generalized cyanosis.

Physical examination reveals his lungs to be clear, and his heart isfound to be within normal limits No cardiac murmurs are heard, and

no cardiopulmonary abnormalities are found Laboratory examinationreveals his CBC, electrolytes, blood urea nitrogen (BUN), and creati-nine to be within normal limits Blood gases reveal a normal oxygentension (PaCO2) and a low arterial oxygen saturation (SaO2) There is

no increase in SaO2with oxygen therapy It was noted when the bloodwas drawn to be sent to the hospital laboratory that it had an unusualchocolate-brown color, and when the blood was exposed to the air itremained an abnormal brown color

10 Which one of the following substances is most responsible for ducing the normal red color of blood?

pro-(A) albumin (D) immunoglobulin

(B) haptoglobin (E) myoglobin

(C) hemoglobin

11 All of the following will cause the hemoglobin – oxygen dissociationcurve to shift to the right and increase the P50 of hemoglobinEXCEPT

(A) an abnormal hemoglobin with decreased oxygen affinity

(B) decreased concentration of 2,3-bisphosphoglycerate

(C) decreased pH

(D) increased P CO2

(E) increased temperature

12 Which one of the following is most likely responsible for the browncolor of this individual’s blood?

(A) an abnormal hemoglobin with decreased oxygen affinity

(B) an abnormal hemoglobin with increased oxygen affinity

(C) carbon monoxide

(D) oxidized hemoglobin

(E) reduced hemoglobin

Case Study V

SICKLE CELL ANEMIA

Integrated Basic Science Content Review

Examination of his peripheral blood reveals abnormal-shaped rocytes and occasional Howell-Jolly bodies Hemoglobin elec-trophoresis reveals 88% hemoglobin S, 8% hemoglobin A2, and 4%hemoglobin F

eryth-13 In comparison to this individual, which one of the following tions of hemoglobin percentages is most consistent with the hemoglo-bin electrophoresis pattern from a normal adult?

14 Which one of the following amino acids has a nonpolar side chain and

is most likely to participate in hydrophobic interactions?

(A) arginine (D) glutamine

(B) asparagine (E) valine

(C) glutamic acid

15 Howell-Jolly bodies are composed of

(A) aggregates of -globin chains (D) remnants of nuclear chromatin (B) aggregates of iron (E) remnants of RNA

notes that sometimes alcohol ingestion will make these episodesworse Physical examination reveals multiple fluid-filled vesicles andbullae on his face, forearms, and dorsa of his hands, along with adiffuse distribution of lanugo-type hair over most of his body Noneurologic abnormalities are found Laboratory examination revealselevated urine levels of uroporphyrin, but no increased levels ofaminolevulinic acid or porphobilinogen Fecal porphyrin is normal.

16 The major sites for the synthesis of heme are the

(A) bone marrow and kidney (D) spleen and bone marrow (B) bone marrow and liver (E) spleen and kidney

(C) liver and kidney

17 Which one of the following biochemical steps is the rate-limiting step

in the biosynthesis of heme?

(A) four molecules of porphobilinogen condense to form uroporphyrinogen III

(B) iron is inserted into protoporphyrin

(C) succinyl CoA combines with glycine to form -aminolevulinic acid (D) two molecules of -aminolevulinic acid condense to form porphobilino- gen

(E) uroporphyrinogen III is converted into coproporphyrinogen III

18 What is the best diagnosis for this individual?

(A) acute intermittent porphyria (D) porphyria cutanea tarda (B) glucose-6-phosphate deficiency (E) sideroblastic anemia

(C) lead poisoning

Case Study VII

of her physical examination are otherwise unremarkable A completeCBC reveals a normocytic normochromic anemia, thrombocytopenia,and neutropenia (pancytopenia) The corrected reticulocyte count is

2%, and polychromasia was not noted The serum blood urea

nitro-gen and creatinine are within normal limits A Coombs’ test is tive A bone marrow biopsy is performed and histologic examinationreveals a fat-to-cell ratio of more than 10 to 1 A few scattered groups

nega-of cells are found consisting mainly nega-of histologically unremarkablelymphocytes and plasma cells No granulomas, fibrosis, or metastaticmalignant cells are found

19 All of the following findings found in a bone marrow specimen fromthe posterior iliac crest of a 40-year-old woman are within normallimits EXCEPT

(A) 1% plasma cells

(B) 10% lymphocytes

(C) a fat to cell ratio of 4 to 1

(D) a myeloid to erythroid ratio of 3 to 1

(E) two megakaryocytes per low-power field

20 Which one of the following substances is a factor that causes theproliferation of granulocytes, monocytes, erythrocytes, and megakary-ocytes?

(A) erythropoietin (D) interleukin 3

(C) GM-CSF

21 What is the best diagnosis for this individual?

(A) aplastic anemia

(B) megaloblastic anemia

(C) microangiopathic hemolytic anemia

(D) myelophthisic anemia

(E) pure red cell aplasia

Case Study VIII

VIII A 42-year-old man presents with left-sided abdominal pain, increasing fatigue, and a low-grade fever.

Physical examination reveals pallor of the skin and a markedlyenlarged spleen A CBC reveals the white blood cell (WBC) count to

be increased to 68,000 cells/L, due mainly to increased numbers of

neutrophils, bands, and metamyelocytes Basophils and eosinophilsare slightly increased in number Other laboratory tests reveal a lowleukocyte alkaline phosphatase (LAP score) and increased serumlevels of vitamin B12 Examination of a bone marrow biopsyspecimen reveals marked hypercellularity (95% cells) due to a

diffuse proliferation of myeloid precursors A differential count ofthese cells reveals all of the neutrophil precursors to be increasedexcept myeloblasts A karyotype from the bone marrow reveals thepresence of a chromosomal translocation 22 to 9 (Philadelphia chro-mosome)

22 Which one of the following cells is a phagocytic leukocyte that tains alkaline phosphatase, collagenase, lactoferrin, and lysozymewithin its specific cytoplasmic granules?

con-(A) basophil (D) monocyte

(B) eosinophil (E) neutrophil

(C) lymphocyte

23 The product of the oncogene c-abl, which is located on chromosome

9 and is translocated in the Philadelphia chromosome, is a

(A) cell surface receptor (D) nuclear regulatory protein (B) growth factor (E) tyrosine kinase

(C) GTP-binding protein

24 What is the best diagnosis for this individual?

(A) adult T cell leukemia/lymphoma (D) hairy cell leukemia

(B) chronic lymphocytic leukemia (E) mycosis fungoides

(C) chronic myelocytic leukemia

25 Which one of the following combinations of histologic characteristicscorrectly describes promyelocytes?

26 One function of myeloperoxidase, an enzyme found in the azurophilicgranules of neutrophils, is to convert

(A) hydrogen peroxide into hydroxyl free radicals in the presence of ferric iron

(B) hydrogen peroxide into hypochlorous acid in the presence of chloride (C) hydrogen peroxide into water

(D) molecular oxygen into superoxide in the presence of NADPH

(E) superoxide into hydrogen peroxide

27 Which one of the following drugs is a pyrimidine antagonist that petitively inhibits DNA polymerase and is useful in treating acutemyelogenous leukemia?

com-(A) cisplatin (D) tamoxifen

(B) cyclophosphamide (E) vincristine

Normal Thymus Histology

T Cell Phenotypes

PATHOLOGY/PHARMACOLOGY/MICROBIOLOGY

Diagnosis

X An 18-year-old man presents with increasing fatigue and pallor.

Physical examination reveals marked pallor of the skin along withsternal tenderness The CBC reveals a normochromic normocytic ane-mia, thrombocytopenia, and a peripheral leukocyte count of 51,000cells/L The majority of these cells have nuclei with immature

chromatin and nucleoli A bone marrow biopsy reveals a hypercellularmarrow due to a diffuse proliferation of immature cells similar tothose seen in the peripheral blood These immature cells have thefollowing characteristics: positive staining for terminal deoxynu-cleotide transferase (TdT), acid phosphatase, CD3, CD5, and CD7;negative staining for myeloperoxidase, surface immunoglobulin (sIg),

cytoplasmic m, CD10, CD15, CD19, and CD30 Additional workup

revealed that this young adult patient has a mediastinal mass

28 Which one of the following is the name given to describe the ture T lymphocytes that differentiate within the thymus?

imma-(A) cortical epithelial cells (D) nurse cells

(B) interdigitating cells (E) thymocytes

(C) medullary epithelial cells

29 Which one of the following phenotypes is most consistent with a Tlymphocyte?

30 What is the correct diagnosis for this patient?

(A) acute myeloblastic leukemia

(B) B cell acute lymphoblastic leukemia

No thymus shadow is seen with x-ray, and the peripheral blood veals marked lymphopenia, as both T lymphocytes and B lympho-cytes are decreased in number Serum immunoglobulins are decreased

re-in amount Extensive workup reveals decreased levels of adenosre-inedeaminase in his RBCs with markedly elevated levels of dATP

31 In which one of the following locations does T lymphocyte tion primarily occur?

matura-(A) bone marrow (D) spleen

(B) bursa of Fabricius (E) thymus

(C) lymph nodes

32 During the breakdown of purine nucleotides to uric acid, adenosinedeaminase directly converts adenosine to

(A) guanine (D) thymine

(B) hypoxanthine (E) xanthine

(C) inosine

33 What is the best diagnosis for this infant?

(A) agammaglobulinemia of Bruton

(B) DiGeorge’s syndrome

(C) isolated deficiency of IgA

(D) severe combined immunodeficiency disease

(E) Wiskott-Aldrich syndrome

Case Study XII

Bone Marrow Findings

XII A 61-year-old man presents with increasing fatigue, weight loss, and bone pain.

Physical examination reveals pallor and focal bone tenderness ination of the peripheral smear reveals that many of the RBCs areadherent to one another like “stacks of coins” (rouleau) Laboratoryexamination reveals increased serum calcium and protein, but normalserum levels of albumin Serum protein electrophoresis reveals asingle large spike in the gamma region X-rays reveal multiplepunched-out lytic lesions, especially in the skull.

Exam-34 Which one of the following leukocytes has an eccentric nucleus thathas radially arranged coarse chromatin and basophilic cytoplasm?

(A) basophils (D) neutrophils

(B) lymphocytes (E) plasma cells

(C) monocytes

35 Digestion of immunoglobulin with papain will produce severalfragments of immunoglobulin Which fragment would contain theantigen-binding portion of immunoglobulin?

(A) kappa chain (D) Fab

(B) lambda chain (E) F(ab) 2

Case Study XIII

peripheral blood reveals the presence of atypical mononuclear cellswith abundant cytoplasm These cells have peripheral condensation ofthe cytoplasm that gives them a “ballerina-skirt” appearance Aheterophil reaction is positive A biopsy specimen from one of theenlarged cervical lymph nodes reveals expansion of the T cell area ofthe node by slightly enlarged lymphocytes with prominent nucleoli(immunoblasts)

37 In which one of the following portions of a lymph node are T cytes the predominate cell?

lympho-(A) cortex (D) medullary sinuses

(B) paracortex (E) primary follicles

(C) germinal centers

38 Endogenously synthesized viral proteins in virus-infected cells arerecognized and attacked by

(A) class I-restricted cytotoxic T cells

(B) class II-restricted helper T cells

(C) class III-restricted B cells

(D) class IV-restricted macrophages

(E) class V-restricted natural killer cells

39 What is the most likely cause of this individual’s disease?

(A) cytomegalovirus (CMV)

(B) Epstein-Barr virus (EBV)

(C) herpes simplex virus (HSV)

(D) human papillomavirus (HPV)

(E) human immunodeficiency virus (HIV)

Case Study XIV

A biopsy specimen from one of these enlarged lymph nodes revealseffacement of the normal lymph node architecture by numerousnodules of uniform size that are found crowded within the cortex andmedulla of the lymph node Within these lymphoid nodules, there is amonotonous neoplastic proliferation of cells.

40 Which group of axillary lymph nodes receives lymph from most ofthe upper limb including the hand?

(A) apical group (D) pectoral group

(B) central group (E) subcapsular group

(C) lateral group

41 Which one of the following processes occurs within the germinalcenters of lymph nodes after B cells have been exposed to a foreignantigen?

(A) The D segment combines with the J segment within

pre-pre-B cells.

(B) Heavy-chain class switching occurs within mature B cells.

(C) IgM is inserted into the surface membrane of immature B cells.

(D) m heavy chains are formed within the cytoplasm of pre-B cells.

(E) Rearrangement of the immunoglobulin heavy-chain gene occurs within precursor B cells.

42 A karyotype of the abnormal cells forming the nodules in the enlargedaxillary lymph nodes in this individual would most likely reveal atranslocation involving

(C) bcr

Bone Marrow Findings

XV A 24-year-old woman presents with severe bleeding from her nose (epistaxis) and multiple pinpoint bleeding spots on her skin.

She states that she had an upper respiratory tract infection about 1week ago when she developed a cough and “runny” nose Physicalexamination reveals multiple, nonpalpable petechiae on her chestand arms No enlarged lymph nodes are found, and neither her livernor the spleen are enlarged The CBC reveals the WBC counts andRBC indices to be within normal limits, but the platelet count is de-creased to 7300 cells/L Her peripheral smear reveals RBCs to be

normochromic and normocytic

43 Endomitosis, which refers to nuclear division without cytoplasmicdivision, is a process that is found in which one of the following types

of cells?

(A) erythroblasts (D) monoblasts

(B) lymphoblasts (E) myeloblasts

(C) megakaryoblasts

44 All of the following substances participate in the formation of theprimary plug of hemostasis by stimulating platelet activationEXCEPT

(B) collagen (E) thromboxane

(C) prostacyclin

45 In considering the differential diagnosis of this individual, which one

of the following is characteristic of immune thrombocytopeniapurpura (ITP) and can be used to distinguish ITP from nonimmunedrug-induced thrombocytopenia?

(A) decreased numbers of megakaryocytes in the bone marrow

(B) increased numbers of megakaryocytes in the bone marrow

(C) monoclonal hypergammaglobulinemia in the peripheral blood

(D) polyclonal hypergammaglobulinemia in the peripheral blood

Physical examination reveals a markedly enlarged spleen along with asmall amount of ascites fluid No enlarged lymph nodes are found ACBC reveals a decreased hematocrit, a normocytic normochromicanemia, thrombocytopenia, and an elevated WBC count Myelocytes,nucleated RBCs, and teardrop-shaped RBCs are found in the periph-eral blood A bone marrow aspiration could not be performed due to a

“dry tap.” The bone marrow biopsy specimen reveals a hypocellularmarrow with increased numbers of megakaryocytes The amount ofmarrow reticulin is markedly increased

46 Which one of the following granules contain substances that are volved in vasoconstriction, platelet aggregation, and platelet adhesion,such as ADP, ATP, ionized calcium, histamine, epinephrine, andserotonin?

in-(A) alpha granules of platelets

(B) azurophilic granules of eosinophils

(C) azurophilic granules of neutrophils

(D) delta granules of platelets

(E) specific granules of neutrophils

47 Platelet-derived growth factor (PDGF) causes fibrosis by binding to aspecific receptor on fibroblasts that

(A) activates tyrosine kinase (D) increases intracellular calcium (B) closes a membrane ion channel (E) inhibits a membrane pump (C) converts GDP to GTP

48 What is the best diagnosis for this individual?

(A) aplastic anemia

(B) chronic myelocytic leukemia

(C) myelofibrosis with myeloid metaplasia

(D) sarcoidosis

(E) splenic hyperplasia

Case Study XVII

XVII A 17-year-old girl presents with menorrhagia.

Obtaining a history you determine that in the past she had a history ofeasy bruising and recurrent nosebleeds, and she had an episode ofuncontrollable bleeding that followed a tooth extraction The results

of her physical examination are essentially unremarkable No malities of her joints are found Laboratory examination reveals aprolonged bleeding time and a slightly prolonged partial thromboplas-tin time (PTT) Quantitative factor VIII levels were decreased alongwith decreased levels of von Willebrand’s factor (vWF) Her plateletcount was normal They appeared unremarkable, but a ristocetinaggregation test was abnormal

abnor-49 In which one of the following parts of a typical platelet are the proteins GpIb and GpIIb/IIIa located?

glyco-(A) alpha granules (D) glycocalyx

(B) dense bodies (E) sol-gel zone

(C) dense tubular system

50 Procoagulant factors produced by endothelial cells include

(F) tissue-type plasminogen activator

51 What is the best diagnosis for this individual?

(A) Glanzmann’s thrombasthenia

(B) hemophilia A

(C) Stein-Leventhal syndrome

(D) Turner’s syndrome

(E) von Willebrand’s disease (vWD)

Case Study XVIII

He does not remember any trauma or injury to his knees This youngboy has a history of easy bruising, especially after minor injuries Healso has had bleeding episodes when his teeth begin to erupt One ofhis mother’s brothers (maternal uncle) bled to death from a toothextraction at an early age Laboratory evaluation reveals normal levels

of vWF and vitamin K, but markedly decreased levels of coagulationfactor VIII The platelet count is within normal limits

52 Coagulation factor VIII is formed in

(A) endothelial cells (D) megakaryocytes

(B) fibroblasts (E) splenic macrophages

(D) conversion of fibrinogen to fibrin

(E) conversion of prothrombin to thrombin

54 Which one of the following combinations of laboratory tests is mostlikely to be present in this young boy?

Answers to Case Study I

1 The answer is B. (Gartner, 2/e, pp 154 – 155 Henry, 19/e, pp 598 – 599.)

The precursor cells of RBCs (erythrocytes) are called erythroblasts In thebone marrow, erythrocyte maturation (erythropoiesis) proceeds through aseries of stages to end with the formation of a mature RBC This normalmaturation sequence is called normoblastic maturation and begins withBFU-E (burst-forming unit – erythroid) cells being stimulated by inter-leukin 3 to form CFU-E (colony-forming unit–erythroid) These cells arethen stimulated by erythropoietin to form proerythroblasts (rubriblasts),which are the first histologically recognizable erythrocyte precursor cells.These cells have immature chromatin, nucleoli, and ferritin in their cyto-plasm In the next stage, the basophilic erythroblast (prorubricyte), thechromatin condenses and the nucleoli disappear Hemoglobin synthesisbegins with the next stage, the polychromatophilic erythroblast (rubri-cyte), as the nucleus continues to condense In the next stage, theorthochromatic erythroblast (metarubricyte), the nucleus is maximallycondensed and the cytoplasm becomes pink due to increasing levels ofhemoglobin The nucleus is then extruded, and the cell becomes a reticu-locyte An example of abnormal erythroid maturation is megaloblasticmaturation, which is characterized by asynchrony between the maturation

of the nucleus and the cytoplasm

2 The answer is B. (Champe, 2/e, pp 326 – 328.)

Megaloblastic anemia is usually caused by a deficiency of either vitaminB12 or folate Vitamin B12 (cobalamin) is involved directly in only twobiochemical reactions in the body: the conversion of homocysteine tomethionine and the isomerization of methylmalonyl coenzyme A (CoA)

to succinyl CoA The conversion of homocysteine to methionine is animportant step in the formation of DNA and involves both vitamin B12and folate Therefore, a deficiency of either of these vitamins will lead toimpaired DNA production and megaloblastic anemia The other biochem-ical step involving vitamin B12, the conversion of methylmalonyl CoA tosuccinyl CoA, is involved in the breakdown of fatty acids with an oddnumber of carbons A deficiency of vitamin B12 theoretically will lead to

a decreased production of normal fatty acids (those with an even number

of carbons, such as palmitate, which has 16 carbons) and an increasedproduction of abnormal fatty acids with an odd number of carbons This