11 Hematology And Oncology Usmle Step 1

Front 1

When B cells and T cells mature, what do they become, respectively?

Back 1

B cells mature into plasma cells whereas T cells become activated T cells

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Front 2

Monocytes develop from what immediate precursor blood cell type?

Back 2

Monoblasts

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Front 3

Promyelocytes, myelocytes, metamyelocytes, and stab cells are precursors for what three granulocytes?

Back 3

Neutrophils, eosinophils, and basophils

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Front 4

Neutrophils, eosinophils, and basophils differentiate from what common precursor blood cell type?

Back 4

Myeloblasts

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Front 5

Reticulocytes are precursors for what type of blood cell?

Back 5

Erythrocytes

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Front 6

Proerythroblasts, lymphoblasts, myeloblasts, monoblasts, and megakaryoblasts share what precursor cell type?

Back 6

Pluripotent hematopoietic stem cells

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Front 7

What precursors indicate that a stem cell has differentiated into the platelet lineage?

Back 7

Megakaryoblasts, which become megakaryocytes that form platelets

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Front 8

Lymphoblasts are the precursors for what two blood cell types?

Back 8

B cells and T cells

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Front 9

In a normal blood sample, name the differential of white blood cells from most to least numerous.

Back 9

Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (remember: Neutrophils Like Making Everything Better)

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Front 10

What molecule do erythrocytes depend upon exclusively for energy?

Back 10

Glucose; remember, they cannot use ketones for energy

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Front 11

What role does the erythrocyte play in acid/base physiology?

Back 11

Erythrocytes carry carbon dioxide from the periphery to the lungs for elimination

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Front 12

How do erythrocytes facilitate transport of carbon dioxide away from the peripheral tissues?

Back 12

The chloride-bicarbonate antiport produces a physiologic chloride shift, resulting in cellular loss of chloride and gain of bicarbonate (and thus carbon dioxide)

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Front 13

What is the average lifespan of an erythrocyte in a normal human host?

Back 13

120 days

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Front 14

What feature of the erythrocyte structure permits easy gas exchange of oxygen and carbon dioxide?

Back 14

The biconcave disc shape permits a high surface area to volume ratio and facilitates gas exchange

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Front 15

How would you describe a peripheral blood smear that shows an increased number of red blood cells and numerous immature red blood cells?

Back 15

There is an erythrocytosis or polycythemia (increased number of cells) and a reticulocytosis (increased immature cells)

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Front 16

Where does an erythrocyte obtain the adenosine triphosphate that it needs for energy?

Back 16

Glucose: 90% is anaerobically degraded to lactate, whereas 10% goes to the hexose monophosphate shunt

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Front 17

How would you describe a peripheral blood smear showing red blood cells of varying sizes and of varying shapes?

Back 17

This smear exhibits anisocytosis (varying sizes) and poikilocytosis (varying shapes)

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Front 18

Where in the body would you typically find the most platelets at any one time?

Back 18

Approximately one third of the platelet pool is stored in the spleen

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Front 19

What is the role of platelets immediately following an injury such as a laceration?

Back 19

Primary hemostasis; for example, they help prevent leakage of red blood cells from damaged vessels

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Front 20

What two types of granules do platelets contain?

Back 20

Dense granules and alpha granules

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Front 21

What are the contents of the dense granules of platelets?

Back 21

Adenosine diphosphate, calcium

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Front 22

You note multiple small red lesions on the skin of a patient that do not blanche with pressure; what are two possible etiologies of these lesions?

Back 22

These are petechiae, which can be caused by a low platelet count (thrombocytopenia) or dysfunctional platelets

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Front 23

What is the life span of a platelet?

Back 23

8-10 days

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Front 24

What happens to platelets when they are in the presence of damaged endothelium?

Back 24

Platelet activation; "sticky" platelets aggregate and interact with fibrinogen to form a hemostatic plug

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Front 25

How do mature platelets form from large megakaryocyte precursors?

Back 25

Small portions of cytoplasm fragment off of megakaryocytes

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Front 26

What are the contents of the α granules of platelets?

Back 26

von Willebrand's factor, fibrinogen

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Front 27

Name three types of granulocytes.

Back 27

Basophils, eosinophils, and neutrophils

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Front 28

What is the main function of leukocytes?

Back 28

To defend against infection

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Front 29

Granulocytes and mononuclear cells are what kind of blood cells?

Back 29

Leukocytes (leuk = white; cyte = cell)

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Front 30

How many leukocytes are normally found per microliter or blood?

Back 30

4000 to 10,000

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Front 31

Name two types of mononuclear cells.

Back 31

Lymphocytes and monocytes

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Front 32

What distinguishes the appearance of a basophil from other granulated cells?

Back 32

The densely basophilic granules, which stain blue with basic stains

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Front 33

What molecules, normally seen as part of the inflammatory cascade, are contained in basophilic granules?

Back 33

Histamine (which causes vasodilation) and other vasoactive amines, as well as leukotrienes (LTD-4)

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Front 34

You note many basophils on a peripheral smear of a patient undergoing an allergic reaction; do you also expect to see mast cells?

Back 34

No; although both cells are involved in allergic reactions, basophils are found in the blood whereas mast cells are typically only found in tissues

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Front 35

What stimulus causes mast cell degranulation?

Back 35

Immunoglobulin E binding to receptors on the surface of the mast cell

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Front 36

What medication can prevent the release of inflammatory compounds from mast cells in a patient with asthma?

Back 36

Cromolyn sodium, which stabilizes mast cell membranes and prevents degranulation

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Front 37

What substances are released when mast cells degranulate?

Back 37

Histamine, heparin, eosinophilic chemotactic factors

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Front 38

Compare and contrast the function and location of basophils and mast cells.

Back 38

Both types of cells mediate allergic reactions and secrete histamine; however, mast cells bind immunoglobulin E and are found in tissue, whereas basophils are found in the blood

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Front 39

Eosinophils are phagocytic cells, particularly in the presence of what?

Back 39

Antigen-antibody complexes

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Front 40

How do eosinophils and mast cells interact during an allergic reaction?

Back 40

Eosinophils produce histaminase and arylsulfatase to limit the inflammatory reaction from mast cell degranulation

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Front 41

Name five diagnoses to consider in a patient discovered to have eosinophilia.

Back 41

Neoplasm, Asthma, Allergic reaction, Collagen vascular disease, Parasites (remember: NAACP)

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Front 42

What distinguishes an eosinophil from other granulated cells?

Back 42

They are full of large, uniform eosinophilic (pink) granules (eosin = a dye that stains pink; philic = loving)

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Front 43

What is the role of major basic protein, found in eosinophils?

Back 43

Major basic protein is released to fight helminth and protozoan infections

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Front 44

A peripheral blood smear shows multiple neutrophils with nuclei that display 6, 7, and even 8 lobes; what lab tests are indicated?

Back 44

B12 and folate tests; hypersegmented polys (neutrophils) are present in deficiencies of either vitamin

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Front 45

What is the appearance of granules found in neutrophils?

Back 45

Large, spherical, azurophilic granules

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Front 46

What are the contents of the granules in neutrophils?

Back 46

Hydrolytic enzymes, lysozyme, myeloperoxidase, and lactoferrin

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Front 47

Under the microscope you note a neutrophil with several granules; what organelle are you looking at?

Back 47

Lysosome

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Front 48

Would you expect to find monocytes in a tissue biopsy?

Back 48

No. Monocytes are found in the blood, not the tissue; when they enter tissue they differentiate into macrophages

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Front 49

Describe the appearance of monocytes.

Back 49

Large, kidney-shaped nucleus; frosted glass cytoplasm

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Front 50

Which cytokine causes activation of macrophages?

Back 50

γ-Interferon

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Front 51

What role do macrophages play in the immunologic response to extracellular pathogens?

Back 51

They are antigen-presenting cells using major histocompatibility complex class II molecules (present phagocytosed extracellular pathogens)

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Front 52

What are dendritic cells in the skin called?

Back 52

Langerhans cells

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Front 53

What molecules do dendritic cells express on their surfaces that are integral to their role as antigen-presenting cells?

Back 53

Major histocompatibility complex II and Fc receptor

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Front 54

What is the major function of B lymphocytes?

Back 54

To produce antibodies

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Front 55

What is the function of T lymphocytes?

Back 55

They control the cellular immune response and regulate the activity of B lymphocytes and macrophages

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Front 56

What kind of antibody response occurs when the body encounters an antigen it has previously seen?

Back 56

Rapidly secreted, previously formed antibodies because B cells have antigenic memory

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Front 57

After maturation, where do B lymphocytes migrate to from the bone marrow?

Back 57

Peripheral lymphoid tissue (lymph node follicles, white pulp of spleen, other uncapsulated lymphoid tissue)

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Front 58

What major histocompatibility complex do B cells possess on the cell surface?

Back 58

Major histocompatibility complex II, which allows B cells to act as antigen-presenting cells

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Front 59

B lymphocytes are part of the _____ (cell-mediated/humoral) immune response.

Back 59

Humoral

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Front 60

What is the response of a B cell after encountering a recognized antigen?

Back 60

B cells differentiate into plasma cells and secrete antibodies

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Front 61

Where do B lymphocytes originate? Where do they mature?

Back 61

They originate and mature in the bone marrow (remember: B = Bone marrow)

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Front 62

You note that a patient's bone marrow shows a monoclonal proliferation of plasma cells; what is the diagnosis?

Back 62

Multiple myeloma

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Front 63

How are plasma cells formed?

Back 63

When B cells encounter a recognized antigen, they differentiate into plasma cells (which have antigenic memory)

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Front 64

What organelles create the appearance of the off-center nucleus and abundant cytoplasm in a plasma cell?

Back 64

The rough endoplasmic reticulum and Golgi apparatus are plentiful (remember: the plasma cell is a protein (antibody) factory!)

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Front 65

What is the site of origin for T lymphocytes? Where do they mature?

Back 65

They originate in the bone marrow but mature in the thymus (remember: T cells mature in the Thymus)

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Front 66

What is the predominate type of lymphocyte found in the circulation?

Back 66

T cells, which make up approximately 80% of circulating lymphocytes

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Front 67

T lymphocytes mediate the _____ (cellular/humoral) immune response.

Back 67

Cellular

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Front 68

Which major histocompatibility complex and CD molecules are expressed by cytotoxic T cells?

Back 68

Major histocompatibility complex I and CD8 (MHC × CD = 8; MHC I × CD8 = 8)

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Front 69

Which major histocompatibility complex and CD molecules are expressed by helper T cells?

Back 69

Major histocompatibility complex II and CD4 (MHC × CD = 8; MHC II × CD4 = 8)

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Front 70

Name the three types of mature cells into which T cells differentiate.

Back 70

Cytotoxic T cells, helper T cells, and suppressor T cells

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Front 71

What is the blood group of an individual with both A and B antigens on red blood cells?

Back 71

Group AB (universal recipient)

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Front 72

What is the blood group of an individual with the B antigen on red blood cells and A antibody in plasma?

Back 72

Group B

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Front 73

What is the blood type of an individual who is a universal recipient of blood cells?

Back 73

Blood group AB; A and B antigen on red blood cells

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Front 74

Which class of antibodies are produced against Rh factor?

Back 74

Immunoglobulin G

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Front 75

A patient receiving a blood transfusion suddenly develops symptoms of anaphylaxis, renal failure, and hypotension and has schistocytes on a smear; what is the likely cause?

Back 75

Incompatible blood type transfusion

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Front 76

If a mother is blood type O and her fetus is blood type B, will the fetus be at risk for hemolytic disease of the newborn?

Back 76

No; antibodies against ABO blood groups are immunoglobulin M class and do not cross the placenta

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Front 77

What happens when an Rh-negative mother with anti-Rh antibodies becomes pregnant with a child who is Rh positive?

Back 77

Erythoblastosis fetalis; the anti-Rh immunoglobulin G crosses the placenta and causes hemolysis in the newborn

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Front 78

What is the blood type of an individual who is a universal donor of blood products?

Back 78

Blood group O; neither A nor B antigens on red blood cells

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Front 79

What is the blood group of an individual with neither A nor B antigens on red blood cells and both A and B antibodies in plasma?

Back 79

Group O (universal donor)

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Front 80

Which class of antibodies are produced against the ABO blood groups?

Back 80

Immunoglobulin M

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Front 81

What is the blood group of an individual with the A antigen on red blood cells and B antibody in plasma?

Back 81

Group A

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Front 82

What happens when an Rh-negative mother is exposed to Rh-positive blood (for instance, during delivery)?

Back 82

Exposure to Rh-positive blood (which has the Rho antigen) will result in the development of anti-Rh immunoglobulin G antibodies, which may complicate future pregnancies

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Front 83

Why do susceptible individuals develop angioedema when taking an angiotensin-converting enzyme inhibitor?

Back 83

Angiotensin-converting enzyme deactivates bradykinin; blocking this results in the unopposed activation of bradykinin by kallikrein

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Front 84

What reaction accounts for the effects of heparin?

Back 84

Heparin activates antithrombin, resulting in inhibition of thrombin and factors IXa, Xa, XIa, and XIIa

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Front 85

What are two stimuli for the conversion of factor X to factor Xa?

Back 85

Activated factor VIIa, or factor IXa with factor VIIIa as a cofactor; this is where the intrinsic and extrinsic pathways converge

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Front 86

Kallikrein links the coagulation cascade to the kinin cascade through its activation of _____ and to the fibrinolytic system through its activation of _____.

Back 86

Bradykinin; plasminogen (to plasmin)

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Front 87

Which coagulation factors are specific to the extrinsic coagulation pathway?

Back 87

Factor VII and tissue factor (thromboplastin)

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Front 88

Once high-molecular-weight kininogen cleaves to form bradykinin, what are the effects of the kinin cascade?

Back 88

Vasodilation, vascular permeability, and pain

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Front 89

Which four reactions is thrombin involved in?

Back 89

Thrombin (IIa) cleaves fibrinogen into fibrin monomers, activates factor XIII to help stabilize and cross-link the fibrin mesh, and activates both factor VIII and factor V

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Front 90

What ion does factor XIII require to stabilize the fibrin mesh?

Back 90

Calcium

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Front 91

Which coagulation factors are specific to the intrinsic coagulation pathway?

Back 91

Factor XII, factor XI, factor IX, and factor VIII

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Front 92

Name two reactions initiated by high-molecular-weight kininogen.

Back 92

High-molecular-weight kininogen is the initial reagent in the kinin cascade and stimulates the coagulation cascade by interacting with factor XII

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Front 93

What factor converts prokallikrein to kallikrein and factor XI to XIa?

Back 93

Factor XIIa; it is thus involved in both the kinin cascade and the coagulation cascade

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Front 94

Which reactions in the coagulation cascade require calcium and a phospholipid surface as cofactors?

Back 94

The conversion of factor IX to IXa, VII to VIIa, X to Xa, and II to IIa

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Front 95

What is the end result of the coagulation cascade?

Back 95

The conversion of fibrinogen into fibrin to form a fibrin mesh that will stabilize the platelet plug

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Front 96

What disorder results from a deficiency of factor IX?

Back 96

Hemophilia B

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Front 97

What does plasmin create when it interacts with fibrin clots?

Back 97

Fibrin split products (fibrin degradation)

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Front 98

Which coagulation factors are common to both the intrinsic and extrinsic coagulation pathways?

Back 98

Factor X, factor V, factor II (prothrombin), and factor XIII

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Front 99

What part of the fibrinolytic system also activates the complement cascade by cleaving C3 to C3a?

Back 99

Plasmin

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Front 100

What disorder results from a deficiency of factor VIII?

Back 100

Hemophilia A

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Front 101

Name two initiators of the intrinsic coagulation pathway.

Back 101

Factor XII is converted to XIIa in the presence of endothelial damage (collagen basement membrane and activated platelets) and by high-molecular-weight kininogen

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Front 102

A patient is severely deficient in vitamin K; which coagulation factors will be affected?

Back 102

This will result in decreased levels of factors II, VII, IX, X, and proteins C and S

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Front 103

Via which molecule does von Willebrand's factor attach to platelets?

Back 103

von Willebrand's factor binds to glycoprotein Ib, found on the platelet surface membrane

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Front 104

Which contributors to thrombogenesis are found within platelets?

Back 104

von Willebrand's factor, fibrinogen, and, upon cyclooxygenase activation of the arachidonic acid cascade, thromboxane A2

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Front 105

What event causes expression of glycoprotein IIa/IIIb on the platelet membrane?

Back 105

Upon adenosine diphosphate activation of the platelet, glycoprotein IIa/IIIb is inserted into the surface membrane

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Front 106

Name four mediators of thrombus formation or degradation that are found within the vascular endothelial cell.

Back 106

von Willebrand's factor, thromboplastin, tissue plasminogen activator, and prostaglandin I2

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Front 107

Which molecule, found on the surface of vascular endothelial cells, is a cofactor in the activation of protein C, an anticoagulant?

Back 107

Thrombomodulin, which is located on the surface of vascular endothelial cells

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Front 108

How do platelets adhere to one another?

Back 108

Glycoprotein IIb/IIIa binds fibrinogen, bridging platelets together

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Front 109

Which molecule binds the subendothelial collagen that is exposed after endothelial damage?

Back 109

von Willebrand's factor binds to the subendothelial collagen and attaches to activated platelets

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Front 110

What is the difference between the function of glycoprotein Ib and glycoprotein IIb/IIIa on the platelet surface?

Back 110

Glycoprotein Ib binds von Willebrand's factor on a damaged endothelial surface, whereas glycoprotein IIa/IIIb binds fibrinogen attached to other platelets

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Front 111

What is the role of protein S in anticoagulation?

Back 111

Protein S is a cofactor for protein C activation, which inactivates factors Va and VIIIa

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Front 112

How does aspirin prevent clot formation?

Back 112

Aspirin inhibits cyclooxygenase in the platelets, thereby preventing TxA2 formation and thus aggregation of platelets

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Front 113

Which medication directly interferes with glycoprotein IIa/IIIb?

Back 113

Abciximab

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Front 114

What is the relationship between von Willebrand's factor and factor VIII?

Back 114

von Willebrand's factor prolongs the half-life of factor VIII, which is why there is an increase in partial thromboplastin time in severe variants of von Willebrand's disease

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Front 115

Which ion helps to strengthen the platelet plug once it has formed?

Back 115

Calcium

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Front 116

Which product of the arachidonic acid pathway favors aggregation of platelets? Which molecules inhibit aggregation?

Back 116

Thromboxane, which is released by platelets, is proaggregation; prostacyclin and nitric oxide, released by endothelial cells, are antiaggregation

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Front 117

Why do neonates receive an injection of vitamin K soon after birth?

Back 117

Neonates lack enteric bacteria that produce vitamin K and can therefore be deficient in the vitamin K-dependent factors and suffer hemorrhagic disease

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Front 118

Name three endogenous factors that initiate anticoagulation.

Back 118

Antithrombin III, protein C, plasminogen

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Front 119

What enzyme is involved in vitamin K activation?

Back 119

Epoxide reductase

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Front 120

How does plasminogen act as an anticoagulant?

Back 120

Plasminogen is activated by tissue plasminogen activator to plasmin, which cleaves the fibrin clot

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Front 121

What process occurs during the adhesion stage of platelet plug formation?

Back 121

The platelet adheres to exposed subendothelial collagen via glycoprotein Ib and von Willebrand's factor

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Front 122

What is the result of the factor V Leiden mutation?

Back 122

The mutation results in a factor V that resists inactivation by activated protein C, leading to a hypercoagulable state

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Front 123

What occurs during the swelling stage of platelet plug formation?

Back 123

The platelet plug "swells" as many platelets bind together secondary to adenosine diphosphate activation of glycoprotein IIa/IIIb bridge formation

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Front 124

How does warfarin act as an anticoagulant?

Back 124

It inhibits epoxide reductase, thereby inhibiting the activation of vitamin K

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Front 125

What is tissue plasminogen activator used for clinically?

Back 125

As a thrombolytic in cases of acute stroke or myocardial infarction within hours of clot formation; tissue plasminogen activator activates plasminogen to plasmin

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Front 126

Which stage of platelet plug formation is affected by ticlopidine and clopidogrel?

Back 126

Swelling; these drugs inhibit the adenosine diphosphate-induced expression of glycoprotein IIa/IIIb

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Front 127

What type of red blood cell morphology would you see in the peripheral blood that is associated with Heinz bodies?

Back 127

Bite cells; the spleen "bites" off the precipitated hemoglobin in the cells

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Front 128

Name two diseases associated with Heinz bodies.

Back 128

α-Thalassemia and glucose-6-phosphate dehydrogenase deficiency

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Front 129

What is the treatment for sideroblastic anemia due to a mutation in δ-ALA synthase?

Back 129

Pyridoxine (vitamin B6)

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Front 130

What symptoms and laboratory findings are consistent with β-thalassemia minor?

Back 130

This condition is asymptomatic, and diagnosed by an hemoglobin A2 > 3.5% on electrophoresis

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Front 131

What x-ray finding should raise your suspicion of β-thalassemia major?

Back 131

Bone marrow expansion, which can be seen as increased marrow space, bone deformities ("chipmunk facies"), and a "crew-cut" appearance of the skull x-ray

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Front 132

What is the role of the mean corpuscular volume in an anemia workup?

Back 132

A mean corpuscular volume < 80 fL is a microcytic anemia; a volume > 100 fL is a macrocytic anemia; a volume between those values is a normocytic anemia

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Front 133

What would you see on hemoglobin electrophoresis in a fetus with deletions of all four α globin genes?

Back 133

Hemoglobin Barts (γ4); this is a lethal condition and will result in hydrops fetalis

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Front 134

What biochemical pathway is interrupted in iron deficiency anemia?

Back 134

The formation of heme (which requires iron)

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Front 135

You see a patient with tongue inflammation and atrophy, dysphagia for solids, and a hemoglobin of 9 g/dL; what is the cause of his anemia?

Back 135

This patient has Plummer-Vinson syndrome, the triad of esophageal webs, atrophic glossitis, and iron deficiency anemia

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Front 136

What is the inheritance pattern associated with a mutation in the δ-aminolevulinic acid gene?

Back 136

This mutation, which causes a hereditary sideroblastic anemia, is found on the X chromosome

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Front 137

What disease do you expect to see in a child born to a father homozygous for hemoglobin S and a mother with β-thalassemia major?

Back 137

This child will be a hemoglobin S/β-thalassemia heterozygote, which presents with mild or moderate sickle cell disease based on β chain production

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Front 138

What condition would you expect to see in a patient with a deletion of three of the four α globin genes?

Back 138

Symptomatic microcytic anemia due to α-thalassemia; known as hemoglobin H disease (β4)

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Front 139

Lead poisoning disrupts which two enzymes involved in the formation of hemoglobin?

Back 139

Lead blocks ferrochelatase and ALA dehydratase, which decreases the synthesis of heme

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Front 140

What are three etiologies of iron-deficiency anemia?

Back 140

Loss (chronic bleeding), malnutrition or poor absorption, and increased demand (such as in pregnancy)

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Front 141

What is the cause of hereditary sideroblastic anemia?

Back 141

A mutation in the δ-aminolevulinic acid gene

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Front 142

What type of mutation is present in a patient with β-thalassemia minor?

Back 142

There is a mutation in one gene (heterozygote), causing underproduction of β globin; the mutation is often in a promoter or splice site

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Front 143

What should you see on hemoglobin electrophoresis in a patient with β-thalassemia (major and minor) that, as in infants, increases the blood's affinity for oxygen?

Back 143

Increased fetal hemoglobin (α2; γ2)

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Front 144

A patient has an elevated serum iron and ferritin, and a normal total iron-binding capacity; what diagnosis should you suspect if a bone marrow aspirate shows blast forms of erythrocytes that have a dark ring around the nucleus?

Back 144

Sideroblastic anemia; the aspirate describes the iron-laden mitochondria that create the appearance of a ringed sideroblast

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Front 145

What is a long-term adverse effect of the treatment of β-thalassemia major?

Back 145

Iron overload (secondary hemochromotosis) due to repeated blood transfusions

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Front 146

What disease, seen in people that live in the Mediterranean region, is caused by point mutations in hemoglobin β chain genes?

Back 146

β-Thalassemia; typically these mutations are at splicing sites and in the promoter regions

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Front 147

A fetus undergoes amniocentesis and is found to have deletions of all four α globin genes; what is the likely outcome?

Back 147

Hydrops fetalis; deletion of four genes is incompatible with life

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Front 148

A mother is concerned that her child has deletions of two α globin genes; what symptoms will likely manifest?

Back 148

Deletion of one or two α globin genes is not associated with symptomatic anemia

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Front 149

What disease, common in Asia and Africa, is caused by deletions of the hemoglobin α chain gene?

Back 149

α-thalassemia; gene deletions result in decreased α globin synthesis

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Front 150

Name two reversible causes of sideroblastic anemia

Back 150

Alcohol use and lead poisoning

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Front 151

What is the cause of basophilic stippling associated with lead poisoning?

Back 151

Lead disrupts the degradation of RNA, which builds up and stains with basic dyes

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Front 152

What treatment is indicated in a patient with β-thalassemia major?

Back 152

Because both genes are mutated, there is no β chain production and the patient requires many blood transfusions

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Front 153

What kind of anemia is associated with congenital deficiencies in purine or pyrimidine synthesis?

Back 153

Macrocytic anemia (eg, orotic aciduria) because of the relative delay in nucleus maturation compared to cytoplasm

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Front 154

Name three ways that heavy alcohol use can cause macrocytic anemia.

Back 154

As a result of vitamin B12 or folate deficiency (malnutrition), liver disease, or by directly affecting red blood cells and causing bone marrow suppression

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Front 155

Name two conditions in which an increased demand for folate can result in a macrocytic anemia.

Back 155

Pregnancy (folate is needed for fetal neural tube development) or hemolytic anemias (folate is needed to replenish hemolyzed blood)

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Front 156

A patient has anemia with a mean corpuscular volume of 110 fL and glossitis and on the peripheral smear you note hypersegmented neutrophils; what are the two possible causes of this condition?

Back 156

B12 or folate deficiency; both present with these features

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Front 157

Why might a patient with Crohn's disease have a macrocytic anemia?

Back 157

Crohn's disease often affects the terminal ileum, the site of vitamin B12 absorption; severe or extensive disease may cause malabsorption of folate as well

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Front 158

What kind of anemia is seen in a patient with poor dietary vitamin intake?

Back 158

Macrocytic anemia, due to B12 or folate deficiency (remember that alcoholics are also often malnourished)

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Front 159

What change in mean corpuscular volume would you expect in an otherwise healthy patient who has had moderate to severe blood loss?

Back 159

Increased mean corpuscular volume, because the patient will compensate with reticulocytosis, which have slightly higher mean corpuscular volumes than mature red blood cells

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Front 160

Why is the mean corpuscular volume increased in megaloblastic macrocytic anemia?

Back 160

There is a defect in DNA synthesis: the nucleus takes longer to mature than the cytosol and thus there is excess cytoplasm, creating a megaloblast; this is caused by B12 and folate deficiency

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Front 161

What is the homocysteine level in patients with B12 and folate deficiency?

Back 161

Both B12 and folate deficiencies have elevated homocysteine levels

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Front 162

Name two drugs than can cause a folate deficiency and macrocytic anemia.

Back 162

Methotrexate or trimethoprim, both of which interfere with folate metabolism

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Front 163

What autoimmune disorder can result in a macrocytic anemia?

Back 163

Pernicious anemia, which results in vitamin B12 deficiency and loss of intrinsic factor

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Front 164

Name five medications that can cause macrocytic anemia.

Back 164

Methotrexate, trimethoprim, fluorouracil, zidovudine, hydroxyurea

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Front 165

Which parasite can cause vitamin B12 deficiency?

Back 165

Diphyllobothrium latum, a tapeworm found in fish

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Front 166

What laboratory test (other than a vitamin level) will distinguish between B12 and folate deficiency as a cause of megaloblastic anemia?

Back 166

Methylmalonic acid is elevated in B12 deficiency but normal in folate deficiency; homocysteine is elevated in both deficiencies

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Front 167

What symptoms can distinguish macrocytic anemia caused by vitamin B12 deficiency and macrocytic anemia caused by folate deficiency?

Back 167

Neurologic symptoms (combined subacute degeneration) are seen in vitamin B12 deficiency but not in folate deficiency because of the role B12 plays in fatty acid pathways

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Front 168

Name three causes of normocytic, normochromic anemia that are not due to hemolysis.

Back 168

Anemia of chronic disease, aplastic anemia (bone marrow failure), renal disease (decreased erythropoietin)

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Front 169

Generally, hemolysis that is intrinsic to the red blood cell occurs in the _____ (intravascular/extravascular) space, whereas hemolysis extrinsic to the red blood cell occurs in the _____ (intravascular/extravascular) space.

Back 169

Extravascular; intravascular. Notable exceptions include paroxysmal nocturnal hemoglobinuria (intrinsic intravascular) and warm agglutinin autoimmune or microangiopathic hemolysis (extrinsic extravascular)

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Front 170

Name six causes of normocytic, normochromic hemolytic anemia that are intrinsic to the red blood cell.

Back 170

Hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, sickle cell anemia, hemoglobin C defect, and paroxysmal nocturnal hemoglobinuria

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Front 171

What is a cause of normocytic, normochromic hemolytic anemia that is intrinsic to the red blood cell and occurs in the intravascular space?

Back 171

Paroxysmal nocturnal hemoglobinuria

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Front 172

Name three causes of normocytic, normochromic hemolytic anemia that are extrinsic to the red blood cell.

Back 172

Autoimmune hemolysis, microangiopathies like disseminated intravascular coagulation or thrombotic thrombocytopenic purpura–hemolytic uremic syndrome, or infections

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Front 173

Name two causes of normocytic, normochromic hemolytic anemia that are extrinsic to the red blood cell and occur in the extravascular space.

Back 173

Autoimmune hemolysis due to warm agglutinins (not cold) or microangiopathies like disseminated intravascular coagulation or thrombotic thrombocytopenic purpura–hemolytic uremic syndrome

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Front 174

How are normocytic, normochromic hemolytic anemias further classified?

Back 174

First by cause: intrinsic vs extrinsic to the red blood cell; and then by location: intravascular vs extravascular

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Front 175

What are two possible explanations for aplastic anemia that is considered idiopathic?

Back 175

There may be an autoimmune etiology or a primary defect in the stem cell itself

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Front 176

You suspect that a patient has aplastic anemia due to an autoimmune process; what treatment can you pursue?

Back 176

Immune suppression using antithymocyte globulin or cyclosporin

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Front 177

What are four viral infections that can cause aplastic anemia?

Back 177

Parvovirus B19 (especially in patients with sickle cell anemia), HIV, Epstein-Barr virus, and viral hepatitis

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Front 178

Name three treatments for aplastic anemia that can be tried when other interventions have failed.

Back 178

Red blood cell and platelet transfusion, dosing with granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor, or allogeneic bone marrow transplantation

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Front 179

How do chronic inflammatory processes cause anemia?

Back 179

The inflammation increases hepcidin levels, which cause macrophages to retain iron, preventing heme from forming

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Front 180

A patient presents with petechiae and bleeding from the gums, fatigue and pallor, and has had several recent infections; a bone marrow aspirate is "dry" making you suspect what process?

Back 180

Aplastic anemia; this patient has symptoms suggestive of thrombocytopenia, anemia, and neutropenia, which are confirmed by the hypocellular aspirate

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Front 181

Why do patients with end-stage renal disease have normocytic, normochromic anemia?

Back 181

The kidneys normally produce erythropoietin; in renal failure the loss of erythropoietin results in anemia, which is amenable to treatment with exogenous erythropoietin

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Front 182

A patient with pancytopenia (anemia, neutropenia, and thrombocytopenia) has fatty infiltrates on bone marrow biopsy; what is the diagnosis?

Back 182

Aplastic anemia; the marrow is depleted, but the cell morphology will be normal

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Front 183

Name four drugs that can result in aplastic anemia.

Back 183

Benzene, chloramphenicol (eg, "gray baby syndrome"), antimetabolites, and alkylating agents (chemotherapy)

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Front 184

What are four general etiologies of aplastic anemia?

Back 184

Radiation or drugs, viral infections, Fanconi's anemia, or idiopathic aplastic anemia

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Front 185

What are the iron, ferritin, and total iron-binding capacity levels in a patient with anemia of chronic disease?

Back 185

Decreased iron and total iron-binding capacity, with increased ferritin

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Front 186

What mechanism of aplastic anemia is seen in patients with Fanconi's anemia?

Back 186

These patients have an inherited defect in DNA repair

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Front 187

What is the inheritance pattern of pyruvate kinase deficiency?

Back 187

Autosomal recessive

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Front 188

What molecule is depleted in the red blood cells of patients that have glucose-6-phosphate dehydrogenase deficiency, leading to anemia?

Back 188

Glutathione; without glucose-6-phosphate dehydrogenase, there is a depletion of glutathione, which results in red blood cell susceptibility to oxidative stress

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Front 189

What organ is responsible for the anemia seen in hereditary spherocytosis?

Back 189

The spleen; the small, inflexible membrane causes the spleen to remove affected red blood cells prematurely

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Front 190

What happens to the hemoglobin in patients with sickle cell disease in the presence of low oxygen concentrations?

Back 190

Without oxygen, the hemoglobin has an exposed charge that causes precipitation and formation of long polymers of hemoglobin that give the characteristic sickle shape to the red blood cell

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Front 191

Name six complications seen in homozygotes for sickle cell disease.

Back 191

Aplastic crisis (parvovirus infection), autosplenectomy, Salmonella osteomyelitis, painful vaso-occlusive crises, renal papillary necrosis, and splenic sequestration crisis

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Front 192

What mutations are present in hereditary spherocytosis?

Back 192

Ankyrin, band 3.1, or spectrin mutations; each normally interacts with the red blood cell skeleton and plasma membrane to preserve normal morphology

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Front 193

Why does the hemolysis seen in paroxysmal nocturnal hemoglobinuria occur in the intravascular space?

Back 193

There is complement-mediated hemolysis, an intravascular process due to decreased levels of decay accelerating factor; decay accelerating factor normally prevents the membrane attack complex from destroying red blood cells

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Front 194

What is the significance of the hemoglobin C mutation?

Back 194

Patients with hemoglobin S and C mutations have milder sickle cell disease than homozygotes for hemoglobin S

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Front 195

You see an African-American patient who has crescent-shaped cells on the peripheral smear; what is the cell and what is the prevalence of this disease?

Back 195

This is a sickle cell; the trait (heterozygotes) occurs in 8% of African-Americans, whereas 0.2% have sickle cell disease (homozygotes)

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Front 196

What x-ray finding in sickle cell anemia may also be seen in thalassemia?

Back 196

The "crew cut" skull radiograph, due to bone marrow expansion, is seen in both conditions

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Front 197

What kind of anemia is seen in patients with hemoglobin C disease?

Back 197

Intrinsic normocytic hemolytic anemia; this condition is due to a mutation in the β globin chain (different from hemoglobin S in sickle cell disease)

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Front 198

What treatment options are available for patients with sickle cell disease?

Back 198

Patients can be treated with hydroxyurea, which increases hemoglobin F concentration, or may undergo allogeneic bone marrow transplantation

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Front 199

Why will a newborn with sickle cell disease initially be asymptomatic?

Back 199

The newborn still has increased levels of hemoglobin F and will be asymptomatic until his hemoglobin F is replaced by hemoglobin S

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Front 200

What is the inheritance pattern seen in glucose-6-phosphate dehydrogenase deficiency?

Back 200

X-linked recessive; therefore, symptoms are usually seen in males

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Front 201

What evolutionary advantage may explain the high prevalence of sickle cell trait in the population?

Back 201

This mutation allows resistance to malaria, an intracellular parasite that infects erythrocytes

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Front 202

What acute process should you suspect in a patient with red blood cells that have no central pallor, increased mean corpuscular hemoglobin concentration, and increased red blood cell distribution width if he contracts a parvovirus B19 infection?

Back 202

Aplastic crisis; this patient likely has hereditary spherocytosis and is predisposed to aplastic anemia during parvovirus infection due to his increased reliance on erythropoiesis

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Front 203

What lab test should you order to confirm the diagnosis in a patient who has spherocytes on the peripheral smear and splenomegaly on exam?

Back 203

Osmotic fragility test; in hereditary spherocytosis the red blood cells will lyse more easily because of decreased membrane flexibility

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Front 204

You see a patient with hereditary spherocytosis but no splenomegaly on exam; if he had Howell-Jolly bodies on peripheral smear what is the reason for your exam and lab findings?

Back 204

This patient has likely had a splenectomy; this treatment can be used if the anemia in hereditary spherocytosis is severe and refractory to treatment

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Front 205

A newborn is born with hemolytic anemia and you determine that there is no blood group or Rh antigen difference between the baby and mother; what congenital error in metabolism may be the cause?

Back 205

Pyruvate kinase deficiency, which causes low adenosine triphosphate in red blood cells and a resultant rigidity of the membranes

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Front 206

A patient develops anemia, indirect hyperbilirubinemia, and jaundice after eating fava beans; what condition should you suspect?

Back 206

Glucose-6-phosphate dehydrogenase deficiency; fava beans, along with sulfa drugs and infections, are well-documented causes of oxidant stress

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Front 207

What is the diagnosis in a patient who has Heinz bodies on the peripheral smear and multiple "bite cells"?

Back 207

Glucose-6-phosphate dehydrogenase deficiency

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Front 208

What is the mutation that causes sickle cell disease?

Back 208

Glutamic acid to valine in the β globin chain

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Front 209

What laboratory test would be abnormal in a patient with paroxysmal nocturnal hemoglobinuria?

Back 209

Increased urine hemosiderin; the hemolysis occurs all day, but urine accumulates overnight and thus appears darker the next day

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Front 210

What vaccinations should be given to patients with sickle cell disease?

Back 210

Vaccinations to encapsulated organisms because of the increased risk of sepsis after autosplenectomy: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis

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Front 211

What type of antibody is involved in autoimmune hemolytic anemia due to warm agglutinins?

Back 211

Immunoglobulin G (remember: Warm weather is GGGreat)

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Front 212

What are two infections that can present with hemolytic anemia due to cold agglutinins?

Back 212

Mycoplasma pneumoniae infection or infectious mononucleosis

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Front 213

What type of hemolytic process causes erythroblastosis fetalis?

Back 213

Warm agglutinin-mediated immune reaction; remember that this is caused by maternal immunoglobulin G antibodies against the fetal Rh group

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Front 214

You note schistocytes or "helmet cells" on the peripheral smear of a patient; what mechanism causes this deformity?

Back 214

This red blood cell morphology is seen in microangiopathic hemolytic anemias, thought to be due to damage as red blood cells pass through a narrow or obstructed vessel lumen

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Front 215

Name two infections that cause hemolysis but are not associated with agglutinins.

Back 215

Intracellular pathogens, like malaria and babesia, can lyse the erythrocyte and cause hemolytic anemia

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Front 216

What does a positive direct Coombs' test represent?

Back 216

A direct Coombs' test adds anti-immunoglobulin G antibodies to the patient's red blood cells; if agglutination occurs, it indicates that the patient's red blood cells are covered with immunoglobulin G antibodies

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Front 217

What are two cardiac pathologies that can cause hemolytic anemia?

Back 217

Severe aortic stenosis, or any mechanical valve, due to the shearing and mechanical destruction of red blood cells

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Front 218

What are four conditions that may be the cause of "helmet cells" or schistocytes on a patient's peripheral blood smear?

Back 218

Disseminated intravascular coagulation, thrombotic thrombocytopenic purpura–hemolytic uremic syndrome, systemic lupus erythematous, or malignant hypertension

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Front 219

What does a positive indirect Coombs' test represent?

Back 219

An indirect Coombs' test adds normal red blood cells to the patient's serum; if agglutination occurs, it indicates that the patient has anti-red blood cell antibodies in serum

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Front 220

Name three conditions that are associated with immunoglobulin G-mediated autoimmune hemolysis.

Back 220

Systemic lupus erythematous, chronic lymphocytic leukemia, and drug reactions (for instance, α-methyldopa)

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Front 221

What type of antibody is involved in autoimmune hemolytic anemia due to cold agglutinins?

Back 221

Immunoglobulin M (remember: Cold ice cream is MMM); cold agglutinins trigger anemia when exposed to cold temperatures

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Front 222

What is the relationship between transferrin and total iron-binding capacity?

Back 222

Total iron-binding capacity is an indirect measure of transferrin, which transports iron in the blood

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Front 223

What are the relevant lab values for a patient with hemochromatosis?

Back 223

The serum iron and ferritin are high and the total iron-binding capacity is low; the percent transferrin saturation is very high

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Front 224

What are the relevant lab values in a patient with iron-deficiency anemia?

Back 224

The serum iron and ferritin are low, whereas the total iron-binding capacity is elevated; the percent transferrin saturation is very low

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Front 225

What changes are seen in serum iron studies for a patient who is either pregnant or using oral contraceptive pills?

Back 225

The serum iron and ferritin are normal; the total iron-binding capacity is elevated due to estrogen exposure (increased binding proteins); the percent transferrin saturation is low

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Front 226

What is the role of ferritin in the body?

Back 226

It is the primary iron storage protein of the body

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Front 227

What are the relevant lab values in a patient with anemia of chronic disease?

Back 227

The serum iron and total iron-binding capacity are low, whereas the ferritin is elevated; the percent transferrin saturation is normal

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Front 228

What is the evolutionary theory behind the etiology of anemia of chronic disease?

Back 228

Pathogens need iron to thrive; sequestration of iron in macrophages may prevent pathogens from reproducing

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Front 229

What cofactor is necessary for the rate-limiting step in heme synthesis?

Back 229

Vitamin B6, which is needed to convert glycine and succinyl-Co-A to aminolevulinic acid

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Front 230

What substrate of heme synthesis accumulates in the blood in lead poisoning?

Back 230

Protoporphyrin

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Front 231

What environmental exposures are common sources of lead poisoning in adults? In children?

Back 231

Adults are exposed to lead in the workplace, such as a battery/ammunition/radiator factories, whereas children are exposed via lead paint

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Front 232

What enzymatic defect is present in acute intermittent porphyria?

Back 232

Porphobilinogen deaminase (also called uroporphyrinogen-I-synthase)

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Front 233

Lead poisoning affects which two enzymes in the heme synthesis pathway?

Back 233

Ferrochelatase and ALA dehydratase are inhibited by lead

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Front 234

How does heme provide negative feedback for its own synthesis?

Back 234

Heme inhibits ALA dehydratase, the second step in heme synthesis

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Front 235

A child presents with a microcytic anemia, gastrointestinal distress, and renal disease; she has developmental regression and basophilic stippling on red blood cells; what is the diagnosis?

Back 235

These are the symptoms of lead poisoning, commonly seen when children are exposed to lead paint

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Front 236

What treatment is available for patients with acute intermittent porphyria?

Back 236

Glucose or heme, both of which inhibit ALA synthase to decrease buildup of heme precursors

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Front 237

What are the differences in neurologic outcomes between adults and children with lead poisoning?

Back 237

Adults typically have headaches, memory loss, and demyelination, whereas children typically have developmental delays

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Front 238

A patient who recently started phenobarbital presents after a day at the beach where she had multiple alcoholic drinks with abdominal pain, polyneuropathy, an altered mental status. Her urine turns pink on standing. What is the diagnosis?

Back 238

Acute intermittent porphyria (remember the five P's: Painful abdomen, Pink urine, Polyneuropathy, Psychological disturbances, Precipitated by drugs [eg, phenobarbital or ethanol])

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Front 239

A patient presents with blisters upon exposure to sunlight and you suspect a porphyria; what is the most likely cause?

Back 239

Porphyria cutanea tarda, the most common porphyria

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Front 240

Which step in heme synthesis requires iron?

Back 240

The final step, where protoporphyrin is converted to heme by ferrochelatase

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Front 241

In porphyria cutanea tarda, there is a defect in the enzyme _____, resulting in an accumulation of _____.

Back 241

Uroporphyrinogen decarboxylase; uroporphyrin, causing "tea-colored" urine

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Front 242

What enzyme is affected in patients with X-linked sideroblastic anemia?

Back 242

δ-ALA synthase, which is responsible for the rate-limiting step of heme synthesis; conversion of glycine and succinyl-Co-A to aminolevulinic acid

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Front 243

What pathologic process occurs if there is a defect in one of the steps of heme synthesis?

Back 243

Porphyria, in which heme precursors accumulate and enter various bodily fluids

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Front 244

What substances accumulate in acute intermittent porphyria?

Back 244

Porphobilinogen, δ-ALA, and uroporphyrin (in the urine)

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Front 245

What condition should be suspected in a patient who has bluish lines on his gums and thick white lines on long bone epiphyses on x-ray?

Back 245

Lead poisoning; the blue lines around teeth are Burton's lines, and the white lines near the epiphysis are lead lines

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Front 246

Name two hematologic manifestations of lead poisoning.

Back 246

Basophilic stippling on erythrocytes and sideroblastic anemia

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Front 247

What treatment is indicated in a child who has lead poisoning?

Back 247

Succimer (remember: it sucks to be a kid who eats lead)

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Front 248

Name three neurologic manifestations of lead poisoning.

Back 248

Encephalopathy, abdominal pain, and wrist and foot drop

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Front 249

What are the main treatments for lead poisoning in adults?

Back 249

Chelation therapy; dimercaprol or EDTA are first-line treatments

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Front 250

What is the role that von Willebrand's multimers play in the development of thrombotic thrombocytopenic purpura?

Back 250

The large von Willebrand's multimers cause increased platelet aggregation (bind glycoprotein Ib) and thrombosis

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Front 251

Glanzmann's thrombasthenia causes a defect in what platelet interaction?

Back 251

Poor platelet-to-platelet aggregation in the platelet plug due to decreased glycoprotein IIb/IIIa

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Front 252

Which platelet disorder has an increased bleeding time but normal platelet count?

Back 252

Glanzmann's thrombasthenia; all have an increased bleeding time, whereas Bernard-Soulier disease, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura have decreased platelet counts

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Front 253

Bernard-Soulier disease causes a defect in the platelet's interaction with what molecule?

Back 253

Endothelial collagen; there is a decrease in the molecule glycoprotein Ib for platelet-to-collagen adhesion

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Front 254

A patient has bleeding from the gums, epistaxis, petechiae, and purpura; what is the likely defect in coagulation?

Back 254

These describe the microhemorrhages associated with a platelet disorder; there may or may not be a decreased number of platelets

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Front 255

A patient develops renal failure, confusion, thrombocytopenia, fever, and schistocytes on peripheral smear; what is the diagnosis?

Back 255

This is the classic pentad of thrombotic thrombocytopenic purpura

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Front 256

What enzyme is deficient in patients with thrombotic thrombocytopenic purpura?

Back 256

ADAMTS-13, a metalloproteinase that degrades von Willebrand's multimers

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Front 257

What is the antibody target in immune thrombocytopenic purpura?

Back 257

Immune thrombocytopenic purpura is caused by antibodies to glycoprotein IIb/IIIa causing platelet destruction

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Front 258

What coagulation test will indicate there is a problem with platelet function?

Back 258

Bleeding time will be increased; there will be no change in prothrombin time or partial thromboplastin time

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Front 259

A patient presents to the emergency room with a large swollen joint tapped and found to be full of blood. He has a history of easy bruising. What condition should you consider in your diagnosis?

Back 259

Spontaneous hemarthrosis, which is a macrohemorrhage seen in hemophilia (compared to petechiae or purpura in platelet disorders)

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Front 260

What are the prothrombin time and partial thromboplastin time results in a patient with hemophilia (A or B)?

Back 260

The prothrombin time will be normal and the partial thromboplastin time will be elevated because hemophilia affects the intrinsic pathway

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Front 261

What coagulation factors are evaluated when you order a prothrombin time test?

Back 261

Factors I, II, V, VII, and X; the extrinsic pathway

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Front 262

What coagulation factors are evaluated when you order a partial thromboplastin time test?

Back 262

All coagulation factors except VII and XIII; the intrinsic pathway

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Front 263

What are the prothrombin time and partial thromboplastin time changes in a patient with vitamin K deficiency?

Back 263

Vitamin K deficiency causes both prothrombin time and partial thromboplastin time elevations

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Front 264

Hemophilia A is caused by a deficiency of _____, whereas hemophilia B (Christmas disease) is caused by a deficiency of _____.

Back 264

Factor VIII; factor IX

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Front 265

What is the most common inherited bleeding disorder?

Back 265

von Willebrand's disease, an autosomal dominant disease that can have varying severity (typically mild)

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Front 266

Name seven causes of disseminated intravascular coagulation.

Back 266

Gram-negative Sepsis, Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome (loss of ATIII), or Transfusion (remember: STOP Making New Thrombi)

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Front 267

Why can you see an elevated partial thromboplastin time in a patient with von Willebrand's disease?

Back 267

von Willebrand's factor carries and protects factor VIII; deficiencies in von Willebrand's factor can cause intrinsic pathway coagulopathies related to factor VIII deficiency

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Front 268

What are the platelet count, bleeding time, prothrombin time, and partial thromboplastin time results of a patient in disseminated intravascular coagulation?

Back 268

Widespread activation of all coagulation pathways results in global depletion: a low platelet count and an increased bleeding time, prothrombin time, and partial thromboplastin time

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Front 269

What are the platelet count, bleeding time, prothrombin time, and partial thromboplastin time in a patient with von Willebrand's disease?

Back 269

There is an elevated bleeding time due to a defect in platelet adhesion; in severe von Willebrand's deficiency, there is also an increase in partial thromboplastin time due to decreased half-life of factor VIII

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Front 270

A patient presents with petechiae and gastrointestinal bleeding; initial labs show schistocytes, elevated fibrin split products, and decreased fibrinogen, factor V, and factor VIII. What condition should you be concerned about?

Back 270

Disseminated intravascular coagulation

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Front 271

Why does protein C or S deficiency lead to a hypercoaguable state?

Back 271

There is an inability to inactivate factors V and VIII

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Front 272

What is the risk associated with administering warfarin in the setting of protein C or S deficiency?

Back 272

Hemorrhagic skin necrosis

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Front 273

What is the pathogenesis of factor V Leiden?

Back 273

There is a mutation in factor V, rendering it unable to be degraded by protein C, leading to a hypercoaguable state

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Front 274

How would a patient with antithrombin III deficiency react to administration of heparin?

Back 274

The patient would not have the expected increase in partial thromboplastin time after heparin administration because heparin's mechanism of action is dependent on AT III

2010-350

Front 275

What is the difference in tumor location between leukemia and lymphoma?

Back 275

In leukemia, tumor cells are typically found in the blood and bone marrow, whereas in lymphoma the tumor cells are lymphoid masses (large lymph nodes)

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Front 276

What demographic group is most affected by Hodgkin's lymphoma?

Back 276

Hodgkin's lymphoma is more common among men and is bimodal, seen in the young and elderly

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Front 277

Which virus is implicated in Hodgkin's lymphoma? Non-Hodgkin's lymphoma?

Back 277

Epstein-Barr virus is associated with 50% of cases of Hodgkin's lymphoma; HIV and other immunosuppressed states are risk factors for non-Hodgkin's lymphoma

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Front 278

Typically, non-Hodgkin's lymphoma is a tumor derived from what type of cell?

Back 278

B lymphocytes, except for the few that have lymphoblastic T-cell origin

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Front 279

What findings on biopsy portend a good prognosis in a patient with Hodgkin's lymphoma?

Back 279

A low number of Reed-Sternberg cells and an increased number of lymphocytes

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Front 280

What malignancy is associated with Reed-Sternberg cells (cells with a distinctive bilobed nucleus that looks like "owl's eyes")?

Back 280

Hodgkin's lymphoma; these cells are necessary but not sufficient for the diagnosis

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Front 281

A patient has night sweats, fevers, weight loss, and new palpable lymph nodes. Which type of lymphoma is more likely: Hodgkin's or non-Hodgkin's?

Back 281

Hodgkin's lymphoma; these are "B" symptoms, more common in Hodgkin's

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Front 282

What pattern of lymph node involvement is seen in Hodgkin's lymphoma? How does this differ from non-Hodgkin's lymphoma?

Back 282

Hodgkin's lymphoma tends to be localized (especially mediastinal) and spread to contiguous nodes, whereas non-Hodgkin's is more likely to be peripheral, with extranodal involvement and noncontiguous spread

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Front 283

Lacunar cells are variants of Reed-Sternberg cells that are found in what variant of Hodgkin's disease?

Back 283

Nodular sclerosing (65% to 75% of all Hodgkin's cases)

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Front 284

What is the CD profile of Reed-Sternberg cells?

Back 284

CD30+ and CD15+

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Front 285

Which type of Hodgkin's lymphoma has a poor prognosis and is most often found in older men with disseminated disease?

Back 285

Lymphocyte depleted (rare)

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Front 286

Which type of Hodgkin's lymphoma has an intermediate prognosis and is marked by numerous Reed-Sternberg cells and lymphocytes?

Back 286

Mixed cellularity (25% of all Hodgkin's cases)

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Front 287

Which two types of Hodgkin's lymphoma have the most favorable prognosis?

Back 287

Nodular sclerosing (65% to 75% of all Hodgkin's cases) and lymphocyte predominant (6% of all Hodgkin's cases)

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Front 288

How does the ratio of Reed-Sternberg cells to lymphocytes correlate with prognosis of Hodgkin's lymphoma?

Back 288

The higher the lymphocyte to Reed-Sternberg cell ratio, the better the prognosis

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Front 289

Histopathology in a 30-year-old female with Hodgkin's lymphoma shows few Reed-Sternberg cells, many lymphocytes, and collagen banding with lacunar cells; what is the lymphoma type?

Back 289

Nodular sclerosing, the most common type of Hodgkin's lymphoma (65% to 75% of all Hodgkin's cases), seen in young adults, in women more than men

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Front 290

What is the histological appearance of Burkitt's lymphoma?

Back 290

Sheets of lymphocytes interspersed with macrophages ("starry-sky" appearance)

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Front 291

What is the gene product of the translocation associated with Burkitt's lymphoma?

Back 291

c-myc oncogene moves next to heavy-chain immunoglobulin gene promoter and is thus produced in large quantities

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Front 292

What infectious etiology is associated with Burkitt's lymphoma?

Back 292

Epstein-Barr virus

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Front 293

Which variant of non-Hodgkin's lymphoma is associated with t(14;18)/bcl-2 expression?

Back 293

Follicular lymphoma (small cleaved cell); bcl-2 inhibits apoptosis in this B-cell lymphoma

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Front 294

A Japanese patient presents to your office with multiple skin lesions and lab tests reveal HTLV-1 infection; what malignancy should you consider?

Back 294

Adult T-cell lymphoma, an aggressive neoplasm seen in regions endemic for HTLV-1: Japan, West Africa, and the Caribbean

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Front 295

What lesion is associated with the endemic form of Burkitt's and where is this lymphoma endemic?

Back 295

Jaw lesions, Africa; in the United States, pelvic or abdominal lesions are often the presenting complaint

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Front 296

What is the prognosis in a patient who has follicular lymphoma?

Back 296

This has a slow, indolent course, but is difficult to cure so it becomes a chronic disease

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Front 297

Lymphoma immunohistochemistry reveals a t(11:14) translocation and CD5 positivity; what is the prognosis?

Back 297

This is mantle cell lymphoma, a type of non-Hodgkin's lymphoma seen in older males that has poor prognosis

2010-352

Front 298

Which variant of non-Hodgkin's lymphoma is associated with t(8;14)/c-myc expression?

Back 298

Burkitt's lymphoma, a B-cell lymphoma

2010-352

Front 299

What translocation is associated with mantle cell lymphoma?

Back 299

t(11;14)

2010-352

Front 300

A patient presents with multiple cutaneous lesions, and a biopsy is consistent with mycosis fungoides; what is the prognosis?

Back 300

Mycosis fungoides, or Sézary syndrome, is a T-cell lymphoma seen in adults that has an indolent course

2010-352

Front 301

Which form of non-Hodgkin's lymphoma can be derived from either B or T cells?

Back 301

Diffuse large-cell lymphoma (80% B-cell, 20% T-cell origin), the most common adult non-Hodgkin's lymphoma

2010-352

Front 302

A patient has a monoclonal spike on protein electrophoresis; what symptoms and imaging would suggest this is due to Waldenstrom's macroglobulinemia rather than multiple myeloma?

Back 302

Waldenstrom's macroglobulinemia is more likely to have symptoms of hyperviscosity due to immunoglobulin M pentamers and does not have bone lesions, unlike myeloma

2010-353

Front 303

What findings on radiograph should elevate your suspicion for multiple myeloma?

Back 303

Round "punched-out" lytic bone lesions

2010-353

Front 304

A patient with multiple myeloma presents with a fever; what dangerous complication of his disease is he at risk for?

Back 304

Infection. Multiple myeloma is an immunosuppressed state: the immunoglobulins produced are nonfunctional and neoplastic plasma cells crowd out functional leukocytes

2010-353

Front 305

A 65-year-old man has a monoclonal immunoglobulin spike on serum protein electrophoresis. He is asymptomatic. What is the likely diagnosis?

Back 305

Monoclonal gammopathy of undetermined significance; the condition may or may not progress to multiple myeloma

2010-353

Front 306

Name a characteristic finding of multiple myeloma that can be seen on peripheral blood smear.

Back 306

Rouleaux formation, in which red blood cells appear to be stacked like poker chips

2010-353

Front 307

What are two minimally invasive tests that can be used to further corroborate the diagnosis in a patient you suspect has multiple myeloma?

Back 307

Bence Jones proteins (immunoglobulin light chain) in the urine, and monoclonal immunoglobulin spike on protein electrophoresis; bone marrow is required for definitive diagnosis

2010-353

Front 308

Compared to Waldenstrom's macroglobulinemia, multiple myeloma predominantly produces which immunoglobulin?

Back 308

Myeloma produces immunoglobulin G (55%) or immunoglobulin A (25%), compared to immunoglobulin M produced in Waldenstrom's macroglobulinemia

2010-353

Front 309

A 55-year-old male undergoes bone marrow biopsy, which reveals a proliferation of plasma cells that have a "fried egg" appearance; what is the diagnosis?

Back 309

This is likely multiple myeloma, a plasma cell neoplasm that is the most common primary bone tumor in patients older than 40-50 years

2010-353

Front 310

What is the etiology of renal failure in multiple myeloma?

Back 310

Immunoglobulin light chains excreted in the urine (Bence Jones proteins) are toxic to renal tubules; the elevated proteins also cause primary (AL) amyloidosis

2010-353

Front 311

A patient presents with lower back pain, and in your work-up you note he has anemia, elevated creatinine, and elevated calcium; what diagnosis should you consider?

Back 311

Multiple myeloma (think CRAB: hyperCalcemia, Renal insufficiency, Anemia, and Bone/Back pain)

2010-353

Front 312

A child presents with a mediastinal mass, and immunohistochemistry reveals a population of cells that are positive for terminal deoxynucleotidyl transferase (TdT) and common acute lymphoblastic leukemia antigen (CALLA); what is the diagnosis?

Back 312

Acute lymphocytic leukemia/lymphoma; TdT is a marker of prelymphocytes

2010-354

Front 313

The peripheral smear of an adult patient has multiple granulated blast forms and you note small, stick-like crystals in the cytoplasm; what is the diagnosis?

Back 313

This patient has myeloblasts (granulated blasts), and Auer rods ("bundles of sticks") consistent with acute myelogenous leukemia

2010-354

Front 314

In the course of chronic myelogenous leukemia, what event causes the beginning of the terminal phase of the illness?

Back 314

Transformation to either acute myelogenous leukemia or acute lymphoblastic leukemia (ALL), termed a "blast crisis"; until this phase, chronic myelogenous leukemia typically follows a more indolent course

2010-354

Front 315

What is the treatment for the M3 type of acute myelogenous leukemia?

Back 315

All-trans retinoic acid, which causes the myeloblasts to differentiate into mature forms

2010-354

Front 316

Bone marrow biopsy of a child with a mediastinal mass and immature white blood cell forms in the peripheral blood reveals an extreme elevation in lymphoblasts; what cell characteristic would portend a better prognosis?

Back 316

Translocation (12;21) conveys a better prognosis; although acute lymphoblastic leukemia (ALL) is generally responsive to chemotherapy

2010-354

Front 317

What diagnosis is confirmed by the presence of the Philadelphia chromosome (t[9;22], bcr-abl)?

Back 317

Chronic myelogenous leukemia

2010-354

Front 318

What lab test can help distinguish between chronic myelogenous leukemia and a leukemoid reaction in a patient with an elevated white blood cell count?

Back 318

Leukocyte alkaline phosphatase; it will be low in chronic myelogenous leukemia and elevated in a leukemoid reaction (exuberant leukocyte response to infection)

2010-354

Front 319

Patients with chronic myelogenous leukemia are most likely to be in what age range?

Back 319

Patients with chronic myelogenous leukemia are typically between the ages of 30 and 60 years

2010-354

Front 320

Patients with acute lymphoblastic leukemia are most likely to be in what age range?

Back 320

Patients with acute lymphoblastic leukemia (ALL) are typically younger than than 15 years of age

2010-354

Front 321

Patients with chronic lymphocytic leukemia are most likely to be in what age range?

Back 321

Patients with chronic lymphocytic leukemia are typically over the age of 60 years

2010-354

Front 322

What is the treatment of choice of chronic myelogenous leukemia?

Back 322

Imatinib, a compound that inhibits the bcr-abl tyrosine kinase

2010-354

Front 323

An elderly male presents with fatigue and you note anemia with a positive Coombs test and smudge cells on the peripheral smear; what is the likely diagnosis?

Back 323

Chronic lymphocytic leukemia (indistinguishable from small lymphocytic lymphoma)

2010-354

Front 324

A patient with massive splenomegaly has a leukocyte count of 100,000 with a differential including elevated neutrophils, metamyelocytes, basophils, and occasional immature myeloid cells; what is the likely diagnosis?

Back 324

Chronic myelogenous leukemia; all myeloid cell lines are increased in this condition

2010-354

Front 325

An elderly patient presents with a mature B-cell tumor that has cells on the peripheral smear with filamentous, hairlike projections; what lab study should you obtain to confirm the diagnosis?

Back 325

Tartrate-resistant acid phosphatase test; the factors suggest hairy cell leukemia, which will stain tartrate-resistant acid phosphatase positive

2010-354

Front 326

In which tissues, outside of the blood and lymphatic system, might neoplastic leukocytes be found in a patient with acute lymphoblastic leukemia (ALL)?

Back 326

ALL often metastasizes to the central nervous system and testes

2010-354

Front 327

A patient has an unregulated proliferation of clonal leukocytes in the bone marrow; what is the effect on circulating red blood cells, white blood cells, and platelets?

Back 327

The patient has leukemia, which crowds the bone marrow causing decreased red blood cells (anemia), decreased mature white blood cells (and variable numbers of circulating white blood cells), and decreased platelets (bleeding risk)

2010-354

Front 328

What are two laboratory tests that would indicate a patient more likely has a leukemoid reaction than leukemia?

Back 328

Increased white blood cell count with a left shift (approximately 80% bands) and increased levels of leukocyte alkaline phosphatase

2010-355

Front 329

What is a complication of treatment of acute promyelocytic leukemia (M3)?

Back 329

Treatment of acute myelogenous leukemia M3 with all-trans retinoic acidretinoic acid can lead to release of Auer rods, which can lead to disseminated intravascular coagulation

2010-355

Front 330

What are Auer rods?

Back 330

Peroxidase-positive cytoplasmic inclusions found in granulocytes and myeloblasts in patients with acute promyelocytic leukemia

2010-355

Front 331

Name the chromosomal translocation associated with promyelocytic leukemia (M3).

Back 331

t(15;17)

2010-355

Front 332

Name the abnormal protein and the chromosomal translocation that are associated with follicular lymphomas.

Back 332

bcl-2; t(14;18)

2010-355

Front 333

Name the chromosomal translocation that is associated with Ewing's sarcoma.

Back 333

t(11;22)

2010-355

Front 334

Name the abnormal protein and the chromosomal translocation that are associated with Burkitt's lymphoma.

Back 334

c-myc; t(8;14)

2010-355

Front 335

Name the abnormal protein and the chromosomal translocation that are associated with chronic myelogenous leukemia.

Back 335

bcr-abl; t(9;22), the "Philadelphia chromosome" (remember: Philadelphia CreaML cheese)

2010-355

Front 336

Name the chromosomal translocation that is associated with mantle cell lymphoma.

Back 336

t(11;14)

2010-355

Front 337

Histiocytosis X can commonly present in three disease patterns known by what names?

Back 337

Letterer-Siwe disease (hepatosplenomegaly and seborrhea), Hand-Schüller-Christian disease (exophthalmos, lytic skull lesions, and diabetes insipidus), or eosinophilic granulomas

2010-355

Front 338

Immunohistochemistry reveals cells that express S-100 and CD1a surface proteins, and you note "tennis racket"-shaped objects in cells on electron microscopy; what is the diagnosis?

Back 338

Histiocytosis X; the "tennis racket" inclusions are Birbeck granules

2010-355

Front 339

From what lineage do the cells that cause histiocytosis X originate?

Back 339

Histiocytosis X is a proliferation of dendritic cells (Langerhans cells) that are from the monocyte lineage

2010-355

Front 340

What myeloproliferative disorders are associated with the JAK2 mutation (involved in hematopoietic signaling)?

Back 340

Polycythemia vera, essential thrombocytosis, myelofibrosis

2010-356

Front 341

What is the basic pathophysiology of polycythemia vera?

Back 341

An abnormal stem cell clone acquires a JAK2 mutation, which allows it to proliferate independent of growth factors

2010-356

Front 342

What are the relative levels of red blood cells, white blood cells, and platelets in myelofibrosis?

Back 342

Decreased in red blood cells with variable levels of white blood cells and platelets

2010-356

Front 343

What are the relative levels of red blood cells, white blood cells, and platelets in polycythemia vera?

Back 343

Increase in all three lines

2010-356

Front 344

What are the relative levels of red blood cells, white blood cells, and platelets in essential thrombocytosis?

Back 344

Increase in platelets, no change in red blood cell and white blood cell levels

2010-356

Front 345

What is the expected erythropoietin level in a patient with polycythemia vera?

Back 345

Low; because of the JAK2 mutation, erythrogenic precursor cells divide independently of erythropoietin, and increased red blood cells provide negative feedback to the kidneys

2010-356

Front 346

What are the relative levels of red blood cells, white blood cells, and platelets in chronic myelogenous leukemia?

Back 346

Decrease in red blood cells, increase in white blood cells and platelets

2010-356

Front 347

Name five clinical uses for heparin.

Back 347

Immediate anticoagulation for pulmonary embolism, stroke, acute coronary syndrome, myocardial infarction, deep vein thrombosis

2010-356

Front 348

What are the benefits of enoxaparin that allow it to be used in the outpatient setting, as opposed to heparin?

Back 348

Enoxaparin can be administered subcutaneously, has a longer half-life, and does not need monitoring

2010-356

Front 349

What difference between heparin and enoxaparin should be considered when there is a concern of excessive anticoagulation?

Back 349

Enoxaparin is not easily reversible, whereas heparin can be reversed by the administration of protamine sulfate; heparin also has a shorter half-life

2010-356

Front 350

How can you rapidly reverse the anticoagulation induced by heparin administration?

Back 350

Give protamine sulfate, a positively charged molecule that binds negatively charged heparin

2010-356

Front 351

What laboratory test can be used to determine if the heparin dose is in the therapeutic range?

Back 351

The partial thromboplastin time, because heparin activates antithrombin III, which is involved in the intrinsic coagulation pathway

2010-356

Front 352

During pregnancy, is heparin or warfarin the preferred method of anticoagulation?

Back 352

Heparin; unlike warfarin, which is a teratogen, heparin does not cross the placenta and thus can be used during pregnancy

2010-356

Front 353

What is the mechanism by which heparin anticoagulates?

Back 353

It catalyzes the activation of antithrombin III and reduces levels of thrombin and factor Xa

2010-356

Front 354

Name four toxicities of heparin.

Back 354

Bleeding, thrombocytopenia, osteoporosis, and drug-drug interactions

2010-356

Front 355

A 70-year-old woman is given prophylactic heparin while hospitalized for pneumonia. Five days later she develops deep vein thromboses and has a low platelet count. What disease is the likely cause of her sudden thrombocytopenic, hypercoagulable state?

Back 355

Heparin-induced thrombocytopenia; this is an antibody-mediated process that destroys some platelets and overactivates those that remain

2010-356

Front 356

Compare enoxaparin and heparin.

Back 356

Enoxaparin is more specific for factor Xa, has higher bioavailability, and 2-4 times longer half-life

2010-356

Front 357

A patient who was started on heparin therapy develops heparin-induced thrombocytopenia; what change should be made to his treatment regimen?

Back 357

Discontinue the heparin and continue anticoagulation using lepirudin or bivalirudin (direct thrombin inhibitors)

2010-356

Front 358

What is the mechanism of action of lepirudin or bivalirudin?

Back 358

These are hirudin derivatives (an anticoagulant produced by leeches) that directly inhibit thrombin

2010-356

Front 359

What is the mechanism by which warfarin anticoagulates?

Back 359

It interferes with normal synthesis and the gamma-carboxylation of the vitamin K-dependent clotting factors II, VII, IX, and X and proteins C and S

2010-357

Front 360

Name four toxicities of warfarin.

Back 360

Bleeding, teratogenic effects (contraindicated in pregnancy), drug-drug interactions, and skin/tissue necrosis

2010-357

Front 361

What is the therapy of choice for patients who require chronic anticoagulation: heparin or warfarin?

Back 361

Warfarin; this is preferred to heparin because it can be administered orally

2010-357

Front 362

How is warfarin metabolized?

Back 362

By the cytochrome P450 pathway in the liver

2010-357

Front 363

What laboratory test is used to determine if a patient taking warfarin is in the therapeutic range?

Back 363

The prothrombin time will be increased because warfarin affects the EXtrinsic pathway (factor VII) (remember: the EX-PresidenT went to WAR(farin))

2010-357

Front 364

What is the difference in the onset of action between heparin and warfarin?

Back 364

Heparin acts within seconds, whereas warfarin has a slow onset dependent on the half-lives of the normal clotting factors

2010-357

Front 365

Describe the treatment of acute warfarin overdose.

Back 365

Intravenous vitamin K and fresh frozen plasma

2010-357

Front 366

What is the difference in administration between heparin and warfarin?

Back 366

Heparin is administered parenterally (intravenously or subcutaneously) whereas warfarin is given orally

2010-357

Front 367

What major complication can be seen from the administration of thrombolytics?

Back 367

Bleeding

2010-358

Front 368

What is the pharmacologic treatment for thrombolytic toxicity?

Back 368

Aminocaproic acid, an inhibitor of fibrinolysis; this medication can also be given to hemophiliacs for dental procedures

2010-358

Front 369

How do thrombolytics affect the prothrombin time, partial thromboplastin time, and platelet count?

Back 369

There is an increase in both the prothrombin time and partial thromboplastin time due to deactivation of thrombin, and no effect on the platelet count

2010-358

Front 370

What is the primary enzymatic reaction that thrombolytics affect?

Back 370

They either directly or indirectly aid the conversion of plasminogen to plasmin, which initiates fibrinolysis

2010-358

Front 371

Name four drugs that can be used to lyse an existing thrombus.

Back 371

Thrombolytics include streptokinase, urokinase, tissue plasminogen activator (alteplase), and anisoylated plasminogen streptokinase activator complex (anistreplase)

2010-358

Front 372

What treatment option can potentially reverse the pathology of an early myocardial infarction or ischemic stroke?

Back 372

Prompt administration of thrombolytics

2010-358

Front 373

Name five contraindications for thrombolytics that are related to increased risk of bleeding.

Back 373

Patients with active bleeding, a history of intracranial bleeding, recent surgery, known bleeding disorders, or severe hypertension

2010-358

Front 374

Which terminal pathway in the coagulation cascade is enhanced by the administration of thrombolytics?

Back 374

Degradation of fibrin and fibrinogen to fibrin-split-products and deactivation of thrombin

2010-358

Front 375

How does abciximab downregulate platelet aggregation?

Back 375

Abciximab is a monoclonal antibody that binds to the glycoprotein receptor IIb/IIIa on activated platelets, thereby preventing aggregation

2010-358

Front 376

Name four clinical effects of aspirin administration.

Back 376

Antipyretic, analgesic, antiinflammatory, and antiplatelet

2010-359

Front 377

Name five common toxicities of aspirin.

Back 377

Gastric ulceration, bleeding, hyperventilation, Reye's syndrome, and tinnitus (cranial nerve VIII)

2010-359

Front 378

What is the effect of aspirin on bleeding time, prothrombin time, and partial thromboplastin time?

Back 378

Aspirin increases bleeding time but has no effect on prothrombin time or partial thromboplastin time (it only affects platelets)

2010-359

Front 379

What is the mechanism of action of aspirin as an anticoagulant?

Back 379

Aspirin acetylates and irreversibly inhibits cyclooxygenase-1 and cyclooxygenase-2 to prevent the conversion of arachidonic acid to thromboxane A2

2010-359

Front 380

What are three common clinical uses of clopidogrel and ticlopidine?

Back 380

Acute coronary syndrome, during coronary stenting, and reducing the incidence or recurrence of thrombotic stroke

2010-359

Front 381

What is the mechanism of action of clopidogrel and ticlopidine?

Back 381

They inhibit platelet aggregation by irreversibly blocking adenosine diphosphate receptors; without adenosine diphosphate activation there is no glycoprotein IIb/IIIa expressed to bind fibrinogen

2010-359

Front 382

Name a potentially life-threatening toxicity of the antiplatelet drug ticlopidine.

Back 382

Neutropenia

2010-359

Front 383

Name the two most common toxicities of abciximab.

Back 383

Bleeding and thrombocytopenia

2010-359

Front 384

Name a monoclonal antibody that binds the glycoprotein IIb/IIIa receptor on activated platelets and that prevents aggregation.

Back 384

Abciximab

2010-359

Front 385

What are clinical uses of abciximab?

Back 385

Coronary artery disease: acute coronary syndromes or during percutaneous transluminal coronary angioplasty

2010-359

Front 386

What occurs during stage G1 of the cell cycle?

Back 386

The synthesis of components that are needed for DNA synthesis

2010-359

Front 387

During which stage of the cell cycle do antimetabolite drugs work?

Back 387

S

2010-359

Front 388

During which stage of the cell cycle do vinca alkaloids and taxols work?

Back 388

M

2010-359

Front 389

During which stages of the cell cycle does etoposide work?

Back 389

S and G2

2010-359

Front 390

What occurs during stage G2 of the cell cycle?

Back 390

The synthesis of components that are needed for mitosis

2010-359

Front 391

What occurs during stage S of the cell cycle?

Back 391

DNA synthesis

2010-359

Front 392

What occurs during stage M of the cell cycle?

Back 392

Mitosis

2010-359

Front 393

During which stage of the cell cycle does bleomycin work?

Back 393

G2

2010-359

Front 394

How do vinca alkaloids exert their antineoplastic effect?

Back 394

They inhibit microtubule formation, which results in an inability of the cell to perform mitosis

2010-359

Front 395

What reaction is inhibited by the administration of 6-mercaptopurine?

Back 395

The synthesis of purines

2010-359

Front 396

What reaction is inhibited by the administration of either methotrexate or fluorouracil?

Back 396

The synthesis of thymidine, a pyrimidine

2010-359

Front 397

How do alkylating agents and cisplatin exert an antineoplastic effect?

Back 397

These agents introduce cross-links in the DNA structure

2010-359

Front 398

Name five antineoplastic drugs that function by damaging DNA.

Back 398

Alkylating agents, cisplatin, dactinomycin, doxorubicin, etoposide

2010-359

Front 399

How does paclitaxel exert its antineoplastic effect?

Back 399

Paclitaxel inhibits microtubule disassembly, which interrupts the dynamic process required for cell division

2010-359

Front 400

Which antineoplastic drugs interfere with DNA by intercalating into the double helix?

Back 400

Doxorubicin, dactinomycin

2010-359

Front 401

Name three antineoplastic drugs that function by interfering with nucleotide synthesis.

Back 401

Methotrexate, fluorouracil, and 6-mercaptopurine

2010-359

Front 402

How does etoposide exert its antineoplastic effect?

Back 402

Etoposide inhibits topoisomerase II, which is needed to relieve DNA supercoils

2010-359

Front 403

Name two antineoplastic drugs that function by interfering with cellular division.

Back 403

Vinca alkaloids, paclitaxel

2010-359

Front 404

What precaution should patients on fluorouracil take, especially in the summer?

Back 404

Sun protection; fluorouracil can cause photosensitivity

2010-360

Front 405

How does cytarabine exert its antineoplastic effect?

Back 405

It is a pyrimidine antagonist, which inhibits DNA polymerase (needed in S phase)

2010-360

Front 406

What adverse effects are seen in patients treated using 6-mercaptopurine or 6-thioguanine?

Back 406

Bone marrow suppression and liver disease; patients on 6-mercaptopurine also often have gastrointestinal complaints

2010-360

Front 407

What drug, used as an antineoplastic agent, is a folic acid analog that works by inhibiting dihydrofolate reductase?

Back 407

Methotrexate; inhibiting dihydrofolate reductase results in less deoxythymidine monophosphate, which is needed for DNA and protein synthesis

2010-360

Front 408

What agent can be administered to reverse the bone marrow suppression seen with methotrexate use?

Back 408

Leucovorin (folinic acid) can be used to "rescue" the bone marrow by competing with methotrexate for binding sites; however, it does not reverse the effects of fluorouracil

2010-360

Front 409

Often given in conjunction with methotrexate, fluorouracil is administered in the treatment of which tumors?

Back 409

Colon cancer and solid tumors (it is a part of the FOLFOX regimen); it is applied topically for basal cell carcinoma

2010-360

Front 410

A patient is given an excessive dose of fluorouracil; what can be administered to the patient to reduce toxicity?

Back 410

Thymidine (remember: folinic acid will not reverse fluorouracil)

2010-360

Front 411

6-mercaptopurine is used in the treatment of what types of cancers?

Back 411

Leukemias and lymphomas (although not used in chronic lymphocytic leukemia or Hodgkin's lymphoma)

2010-360

Front 412

Name four cancers that methotrexate can be used to treat.

Back 412

Leukemias, lymphomas, choriocarcinomas, and sarcomas (all have many dividing tumor cells)

2010-360

Front 413

What neoplasms are commonly treated using cytarabine?

Back 413

Cytarabine is used to treat leukemias and lymphomas (acute myelogenous leukemia, acute lymphoblastic leukemia, and high-grade non-Hodgkin's lymphoma)

2010-360

Front 414

Other than myelosuppression, what are three toxicities of treatment with methotrexate?

Back 414

Patients can develop a painful mucositis and microvesicular fatty changes in the liver, and it is a teratogen (remember: used for abortion in ectopic pregnancy)

2010-360

Front 415

Name three nonneoplastic conditions in which methotrexate can be used.

Back 415

Abortion in ectopic pregnancy (blocks cell proliferation), rheumatoid arthritis, and psoriasis (decreased immune proliferation and response)

2010-360

Front 416

What are three adverse effects seen in the use of cytarabine?

Back 416

Leukopenia, thrombocytopenia, and megaloblastic anemia

2010-360

Front 417

Which disease is treated using 6-thioguanine?

Back 417

Acute lymphoblastic leukemia

2010-360

Front 418

You are treating a patient with leukemia and are considering using either 6-mercaptopurine or 6-thioguanine. Which should be used if you are also going to treat with allopurinol to prevent tumor lysis syndrome?

Back 418

6-thioguanine; 6-mercaptopurine is metabolized by xanthine oxidase, the enzyme blocked by allopurinol and may thus reach toxic levels if given together

2010-360

Front 419

What is the mechanism by which 6-mercaptopurine and 6-thioguanine exert an antineoplastic effect?

Back 419

These are purine analogs, which inhibit de novo purine synthesis; they are activated by hypoxanthine-guanine phosphoribosyltransferase

2010-360

Front 420

What enzyme is inhibited by the 5F-dUMP/folic acid complex?

Back 420

This complex inhibits thymidylate synthase, which is needed to form deoxythymidine monophosphate for DNA and protein synthesis

2010-360

Front 421

How does fluorouracil, a pyrimidine, interact with folic acid?

Back 421

Fluorouracil is converted to 5F-dUMP, which covalently binds folic acid rendering it ineffective (noncompetitive inhibition)

2010-360

Front 422

Which chemotherapeutic drugs are most likely to cause alopecia as an adverse effect?

Back 422

Doxorubicin, daunorubicin, and etoposide

2010-361

Front 423

After several rounds of chemotherapy, a patient complains of severe dyspnea and your exam fails to find symptoms of heart failure; what antitumor antibiotic is likely a part of his chemotherapy regimen?

Back 423

Bleomycin, an antineoplastic agent that has the well-documented adverse effect of pulmonary fibrosis; you may also see skin changes as an adverse effect

2010-361

Front 424

Which of the antitumor antibiotics has the least myelosuppression as an adverse effect?

Back 424

Bleomycin; myelosuppression is a common adverse effect of all other antitumor antibiotics

2010-361

Front 425

What are three neoplasms in which dactinomycin is commonly used?

Back 425

Ewing sarcoma, Wilms' tumor, and rhabdomyosarcoma (think of childhood tumors: ACTinomycin D because children ACT out)

2010-361

Front 426

A patient presents late in the course of chemotherapy treatments with new symptoms of heart failure; what antineoplastic drug was likely a part of his regimen?

Back 426

Doxorubicin and daunorubicin are notorious for dose-dependent cardiotoxicity; patients may also develop alopecia or other tissue toxicity

2010-361

Front 427

Name three neoplasms commonly treated using etoposide.

Back 427

Small-cell carcinoma of the lung, small-cell carcinoma of the prostate, and testicular cancer

2010-361

Front 428

Which malignancies are commonly treated with doxorubicin or daunorubicin?

Back 428

Hodgkin's lymphoma (the A in the ABVD regimen), myeloma, sarcoma, and solid tumors like breast, lung, or ovarian cancer

2010-361

Front 429

Name two neoplasms commonly treated with bleomycin.

Back 429

Testicular cancer and Hodgkin's lymphoma (the B in the ABVD regimen)

2010-361

Front 430

When does etoposide interfere with the cell cycle?

Back 430

Between G2 and S phase; etoposide inhibits topoisomerase II, which is needed to uncoil DNA strands and synthesize a sister chromatid

2010-361

Front 431

Name three antineoplastic drugs that function by intercalating into DNA strands.

Back 431

Dactinomycin (actinomycin D), daunorubicin, and doxorubicin work by intercalating in DNA strands, causing structural and functional distortions

2010-361

Front 432

What common mechanism is seen in the antineoplastic drugs bleomycin, daunorubicin, and doxorubicin?

Back 432

These drugs generate free radicals, which can cause DNA strand breaks and halt cell replication

2010-361

Front 433

Which alkylating agents are effective at penetrating the blood-brain barrier to access the central nervous system?

Back 433

Nitrosoureas, including carmustine, lomustine, semustine, and streptozotocin

2010-361

Front 434

Which alkylating agents are used especially in treating central nervous system neoplasms?

Back 434

Nitrosoureas; since they penetrate the blood-brain barrier they are used to treat brain tumors like glioblastoma multiforme, but also have central nervous system toxicities like dizziness and ataxia

2010-361

Front 435

Which alkylating agent requires activation by the liver (and thus might not be effective in a patient with liver failure)?

Back 435

Cyclophosphamide or ifosfamide; these cause DNA crosslinks at the 7 position of guanine

2010-361

Front 436

What toxicity is common to both busulfan and bleomycin?

Back 436

Pulmonary fibrosis; both busulfan and bleomycin can result in lung disease

2010-361

Front 437

A patient who has been receiving chemotherapy for breast cancer presents with dark urine and is found to have many red blood cells in urine; this could have been avoided using what medication?

Back 437

Mesna; this patient has hemorrhagic cystitis from cyclophosphamide use

2010-361

Front 438

Which alkylating agent would you choose in a patient about to undergo hematopoietic stem cell transplantation?

Back 438

Busulfan, which will ablate the host bone marrow before transplantation; it is also used in the treatment of chronic myelogenous leukemia

2010-361

Front 439

Cyclophosphamide and ifosfamide are commonly used to treat which conditions?

Back 439

These are used in breast cancer, ovarian cancer, and non-Hodgkin's lymphoma; they are also used at lower doses as immunosuppressants

2010-361

Front 440

What toxicities are associated with vincristine treatment?

Back 440

Neurotoxicity, including areflexia and peripheral neuritis, as well as paralytic ileus

2010-362

Front 441

Which neoplasms are commonly treated using taxols?

Back 441

Breast and ovarian carcinomas

2010-362

Front 442

What antineoplastic drug functions by hyperstabilizing the mitotic spindle so that tumor cells are unable to complete anaphase?

Back 442

PacliTAXel or other TAXols (remember: it is TAXing to stay polymerized [the microtubule stays polymerized])

2010-362

Front 443

Which antineoplastic drugs bind to tubulin during the M phase, inhibiting the formation of microtubules?

Back 443

Vincristine or vinblastine; microtubules are the vines of your cells, and without them the mitotic spindle cannot form

2010-362

Front 444

What toxicity is associated with vinblastine treatment?

Back 444

Bone marrow suppression (remember: vinBLASTine BLASTs Bone marrow)

2010-362

Front 445

Name three neoplasms commonly treated using a vinca alkaloid (vincristine or vinblastine).

Back 445

Hodgkin's lymphoma (the MOPP regimen contains vincristine), Wilms' tumor, and choriocarcinoma

2010-362

Front 446

What are the clinical uses of cisplatin and carboplatin?

Back 446

Testicular, bladder, ovary, and lung carcinomas

2010-362

Front 447

Name two major toxicities of cisplatin and carboplatin.

Back 447

Nephrotoxicity and acoustic nerve damage

2010-362

Front 448

Which drug inhibits ribonucleotide reductase, acting during the S phase to decrease DNA synthesis?

Back 448

Hydroxyurea

2010-362

Front 449

What are the three clinical uses for hydroxyurea?

Back 449

Melanoma, chronic myelogenous leukemia, and sickle cell disease (hydroxyurea increases concentration of hemoglobin F)

2010-362

Front 450

Which cancers have prednisone as part of their treatment regimen?

Back 450

Chronic lymphocytic leukemia, Hodgkin's lymphoma (MOPP regimen)

2010-362

Front 451

How is prednisone thought to exert an antineoplastic effect?

Back 451

Prednisone is thought to induce apoptosis, and may even affect nondividing cells

2010-362

Front 452

What is the most commonly used glucocorticoid in cancer chemotherapy?

Back 452

Prednisone

2010-362

Front 453

A postmenopausal woman who recently started on a selective estrogen receptor modulator for breast cancer complains of vaginal spotting; what condition should you be concerned about?

Back 453

Endometrial carcinoma; because of its partial agonist effects, tamoxifen increases the risk of endometrial carcinoma; raloxifene does not increase the risk of endometrial carcinoma

2010-362

Front 454

What is the primary mechanism of action of tamoxifen and raloxifene?

Back 454

They are selective estrogen receptor modulators that block binding of estrogen to estrogen-receptor-positive cells

2010-362

Front 455

Name two selective estrogen receptor modulators that are used to treat breast cancer.

Back 455

Tamoxifen and raloxifene

2010-362

Front 456

Why is raloxifene not associated with an increased risk of endometrial carcinoma?

Back 456

Raloxifene acts as an antagonist at the level of the endometrium; tamoxifen acts as an agonist (increasing endometrial cancer risk)

2010-362

Front 457

The presence of what tumor marker would prompt you to use tamoxifen in the treatment of breast cancer?

Back 457

Selective estrogen receptor modulators, like tamoxifen, act on the estrogen receptor, so the tumor should be estrogen receptor positive

2010-362

Front 458

What is the proposed mechanism of action of trastuzumab?

Back 458

Helps kills breast cancer cells that overexpress HER-2, possibly through antibody-dependent cytotoxicity

2010-363

Front 459

What treatment option is available in a patient who has metastatic breast cancer that is HER-2/erb-B2 positive?

Back 459

Trastuzumab, a monoclonal antibody against HER-2

2010-363

Front 460

What organ should be monitored closely for adverse effects in a patient taking trastuzumab?

Back 460

The heart; an adverse effect of trastuzumab therapy is cardiotoxicity

2010-363

Front 461

What is the mechanism of action of imatinib?

Back 461

This molecule binds to and inhibits the tyrosine kinase formed by the bcr-abl translocation found in chronic myelogenous leukemia

2010-363

Front 462

What are the clinical uses for imatinib?

Back 462

Chronic myelogenous leukemia and gastrointestinal stromal tumors (both express the bcr-abl tyrosine kinase)

2010-363