Inflammation & Repair Flashcards

1
Q
  1. A researcher is studying acute inflammation.
    Specifically, he has designed an antibody that binds
    to and blocks the activity of one of the Toll-like
    receptors. When the antibody is used, which step in
    acute inflammation would be directly blocked?
    A. Identification of the inciting agent
    B. Recruitment of white blood cells
    C. Removal of the inciting agent
    D. Regulatory steps to maintain control of the
    inflammatory response
    E. Resolution of the inflammation
A
  1. Correct: Identification of the inciting agent (A)
    The five possible answers listed are the five general
    steps of acute inflammation in order from start to
    finish. The Toll-like receptors are important in allowing
    immune cells to identify the agent that is precipitating
    the acute inflammation (A). For (B-E), see
    previous discussion.
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2
Q
  1. The hospital laboratory receives a specimen
    from a clinical physician for analysis. The specimen
    vial contains a watery fluid. Testing indicates a very
    low concentration of protein, and only a very few red
    and white blood cells are identified on microscopic
    examination. Of the following disease types, which
    is the most likely source of the fluid collection from
    which this sample was obtained?
    A. Acute appendicitis
    B. Subdural hematoma
    C. Bronchopneumonia
    D. Congestive heart failure
    E. Acute pancreatitis
    F. Sepsis
A
  1. Correct: Congestive heart failure (D)
    The fluid described is a transudate, which would produce a serous effusion in a body cavity. A serous effusion is one that is watery, clear, and light yellow in color.
    Transudates are produced by either high intravascular
    pressures, such as would occur with congestive heart
    failure (D), or with low oncotic pressure, such as in
    hypoalbuminemia. With high intravascular pressure,
    fluid is essentially forced out of the vasculature into the body cavity or soft tissue, whereas with hypoalbuminemia,
    the oncotic pressure of the blood, which is the
    force that draws fluid back into the vasculature from
    the soft tissue, is low. Hypoalbuminemia can occur in liver failure, because of decreased production of albumin,
    or in nephrotic syndrome, because of loss of albumin
    in the urine. The other choices would cause an
    exudate, which has a high concentration of protein and
    a prominent cellular component (A-C, E-F).
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3
Q
  1. A 6-year-old boy falls off his bicycle while in
    the driveway of his house. His mother witnesses
    him fall and sees that he strikes his knee against the
    ground but does not hit his head. She feels that he
    is fine and returns to her work. About 20 minutes
    later, he comes in the house to get a drink of water.
    She can see that the skin on his knee where he hit
    the ground is intact but red. The red discoloration of
    the skin is not a bruise. Of the following mediators,
    which played the largest role in producing this visible
    change in the skin?
    A. ICAM-1
    B. PECAM-1
    C. Histamine
    D. Thromboxane A2
    E. E-selectin
    F. P-selectin
A
  1. Correct: Histamine (C)
    Histamine plays a large role in vasodilation, and vasodilation produces the erythema (red discoloration)
    and heat usually associated with acute inflammation
    (C). Thromboxane A2 causes vasoconstriction (D),
    and the other mediators listed (A-B, E-F) participate
    in the migration of white blood cells through the wall
    of the blood vessel to the site of the inflammation.
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4
Q
  1. A researcher is studying acute inflammation
    and has developed an antibody for her research. This
    antibody, called ILF-2, binds to a receptor on the
    endothelial cell and blocks it. Binding of the antibody
    causes impairment of leukocyte rolling, though
    margination still occurs. Of the following receptors,
    which is ILF-2 most likely binding to?
    A. E-selectin
    B. L-selectin
    C. ICAM-1
    D. PECAM-1
    E. Integrin
    F. Sialyl-Lewis-X
A
  1. Correct: E-selectin (A)
    L-selectin and Sialyl-Lewis-X are found on the leukocytes
    (B, F). Integrins (on leukocytes) and ICAM-1 (on endothelial cells) participate in tight adhesion of the white blood cell to the vessel wall (C, E), and PECAM-1 participates in transmigration of the white blood cell through the wall of the vessel (D). E-selectin is found on endothelial cells and participates in leukocyte rolling and adhesion (A).
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5
Q
  1. A medical student is writing a paper on opsonins.
    In the paper, the student lists the various opsonins and
    the appropriate receptor that they bind to. In reading
    the paper, the student’s professor identifies one
    mispairing. Of the following pairings, which represents
    an opsonin and the wrong receptor for that opsonin?
    A. Integrin and ICAM-1
    B. IgG and the Fc Receptor
    C. CD34 and L-selectin
    D. C1q and collectins
    E. Complement receptors (1 and 3) and C9
A
  1. Correct: Complement receptors (1 and 3) and
    C9 (E)
    Opsonin is a general term for a group of molecules
    that bind to bacteria and dead cells and allow for their
    recognition by leukocytes as something needing to be
    ingested and destroyed. The opsonins are IgG, fragments
    of C3, and collectins. IgG binds to the Fc receptor
    (B), and collectins bind to C1q, (D) but fragments
    of C3 bind to complement receptors (E). Integrin and
    ICAM-1 and CD34 and L-selectin are appropriately
    paired (A, C), but none of these mediators are opsonins.
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6
Q
  1. A medical student in a laboratory is studying
    the effects of a drug that irreversibly binds to and
    inhibits the function of ICAM-1. When the drug
    is administered, the student observes that acute
    inflammation is impaired. Of the following, which
    protein is also indirectly involved?
    A. Sialyl-Lewis-X
    B. L-selectin
    C. CD11/CD18 integrins
    D. VLA-4
    E. CD 31
A
  1. Correct: CD11/CD18 integrins (C)
    During the process of firm adhesion and transmigration,
    CD11/CD18 on the leukocyte binds to ICAM-1 (C). Sialyl-Lewis-X binds to P-selectin and E-selectin, L-selectin binds to GlyCam-1 and CD34, VLA-4 binds to VCAM-1, and CD31 on endothelial cells binds to CD31 on white blood cells.
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7
Q
  1. The parents of a young child bring him to a pediatric
    hospital for evaluation. Their son has frequently
    sustained middle ear infections and has had two episodes
    of pneumonia, both requiring hospitalization.
    Testing indicates that the child has a deficiency in the
    β subunit of CD18. Which of the following diseases
    does the child have?
    A. Leukocyte adhesion deficiency type 1
    B. Leukocyte adhesion deficiency type 2
    C. Chronic granulomatous disease
    D. Chediak-Higashi
    E. Cryopyrin-associated periodic fever syndromes
A
  1. Correct: Leukocyte adhesion deficiency type 1
    (LAD-1) (A)
    LAD-1 is due to a defective production of the β subunit
    of CD18 (A). LAD-2 is due to absence of sialyl-
    Lewis-X (B). Chronic granulomatous disease is due to
    impaired phagocyte oxidase production (C). Chediak-
    Higashi syndrome is due to a mutation of CHS1, a
    lysosomal trafficking regulator (D). Cryopyrin-associated
    periodic fever syndromes are due to gain-of-function
    mutations affecting the inflammasome (E).
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8
Q
  1. A 56-year-old male experiences “crushing”
    substernal chest pain and is taken by private vehicle
    to the emergency department of the local hospital.
    A troponin-I test performed in the emergency
    room indicates a concentration of 0.01 ng/mL, and
    a 12-lead electrocardiogram (ECG) shows ST elevation
    in the anterior leads. Streptokinase is administered
    within 20 minutes of the onset of symptoms
    and the patient’s symptoms resolve. A repeat ECG
    after administration of the drug is normal. Given
    that some degree of acute inflammation occurred in
    this process, of the following, which is the most likely
    outcome in the myocardium?
    A. Resolution
    B. Chronic inflammation
    C. Scarring
    D. Prolonged pericardial effusion
    E. Abscess formation
A
  1. Correct: Resolution (A)
    Although the individual was sustaining an acute
    myocardial infarct, a presumptive diagnosis was
    made, and restoration of blood flow was made prior
    to irreversible damage; therefore, resolution of the
    inflammation is likely (A). If the troponin I had been
    elevated, it would indicate irreversible damage. As
    the cardiac myocytes are essentially incapable of
    division, the necrotic cells would have triggered
    acute inflammation; however, complete resolution is
    impossible without the potential for division among
    the surviving cells. In that case, scarring would be
    the result (C). As the underlying etiologic cause is
    neither infectious nor otherwise likely to linger in
    the tissue, chronic inflammation, a prolonged effusion,
    or an abscess would not occur (B, D-E).
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9
Q
  1. A 35-year-old female is involved in a motor
    vehicle accident during which she is thrown against
    the steering wheel after the airbag fails to deploy,
    causing her to sustain a laceration of her liver. She
    is treated nonoperatively and is told at her 6 month
    check-up that she has had complete resolution of the
    damage to her liver. Assuming this statement is correct,
    which of the following could be identified histologically
    in the region of the liver where the injury
    occurred?
    A. Extensive fibrosis
    B. Wavy fibrosis between hepatocytes
    C. Increased numbers of blood vessels
    D. Multiple foci of neutrophils
    E. Hemosiderin-laden macrophages
A
  1. Correct: Hemosiderin-laden macrophages (E)
    As a laceration occurred, hemorrhage is expected, and
    when the red blood cells break down, hemosiderin is
    deposited (E). With complete resolution, all injured
    cells are replaced, and inflammatory mediators,
    including inflammatory cells, are no longer present
    (D). During complete resolution, fibrosis would not be
    deposited (A-B). Increased numbers of blood vessels
    are also indicative of chronic inflammation (C).
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10
Q
  1. A 12-year-old male with no past medical history
    is brought to the emergency room by his parents
    because of flu-like symptoms, including cough,
    fever, and general malaise, which are associated with
    the recent development of shortness of breath. During
    his evaluation, an ultrasound of the chest reveals
    a large pericardial effusion, which produces right
    ventricular collapse during diastole. A pericardiocentesis
    is performed, removing ~ 200 mL of translucent,
    watery yellow fluid. Of the following, which is
    the most likely source of the fluid around the heart?
    A. A metastatic pediatric neoplasm
    B. A parasite
    C. A viral infection
    D. A bacterial infection
    E. A fungal infection
A
  1. Correct: A viral infection (C)
    The effusion as described, being watery, translucent,
    and yellow, is a serous effusion, which can be found
    in viral infections (C). Given the clinical scenario, the
    patient most likely has a viral myocarditis or viral
    pericarditis, both of which are commonly due to Coxsackie virus infection. Bacteria, fungi, and parasites are more likely to produce a fibrinous or suppurative
    inflammation (B, D-E), in which case the effusion
    would be less watery, and cloudy, not translucent,
    and a metastatic neoplasm would be more likely to
    produce a fibrinous or even hemorrhagic effusion (A).
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11
Q
  1. A 23-year-old female falls off her bike and
    strikes her thigh against the sidewalk. Bruising
    occurs at the site of impact, and, within minutes, the
    tissue expands at this point, creating a noticeable
    bulge in the skin. Of the following mediators, which
    most directly and significantly played a role in these
    changes?
    A. Reactive oxygen species
    B. Serotonin
    C. Thromboxane A2
    D. Prostaglandins D2
    E. Leukotriene B4
A
  1. Correct: Prostaglandin D2 (D)
    Prostaglandins D2 and E2 cause increased vasculature
    permeability and vasodilation, both of which
    would contribute to fluid leaving the vascular space,
    entering the tissue, and producing swelling (D).
    Serotonin and thromboxane A2 cause vasoconstriction,
    which would impede the changes described
    (B-C), and leukotriene B4 is a chemotactic agent (E),
    responsible for helping recruit white blood cells to
    the site of inflammation. Reactive oxygen species are
    produced as a tool to destroy invading bacteria (A).
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12
Q
  1. A 24-year-old female develops bacterial
    meningitis due to Neisseria meningitidis. On her
    initial presentation to the emergency room, being
    brought in by her family, she is in obvious distress
    and has a fever of 103°F. Laboratory testing indicates
    a white blood cell count of 15,000 cells/μL. Of
    the following mediators, which is least responsible
    for her symptoms, physical examination, and laboratory
    findings?
    A. IL-1
    B. IL-6
    C. IL-12
    D. TNF
    E. CXC chemokines
A
  1. Correct: IL-12 (C)
    The patient has bacterial meningitis, an acute process.
    IL-1, IL-6, and TNF play a role in acute inflammation,
    acting on endothelium to increase adhesion
    molecule expression, activating white blood cells,
    and promoting systemic effects such as fever, elevation
    of acute phase proteins, and increasing leukocyte production. Chemokines recruit white blood
    cells to the site of acute inflammation (A-B, D-E).
    Therefore, in an acute bacterial meningitis, IL-1, IL-6,
    TNF, and CXC chemokines would all play a role; however,
    IL-12 functions mostly in chronic inflammation
    and would not play a role in the acute process (C).
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13
Q
  1. A 2-year-old boy with recurrent infections
    is found to improperly synthesize NADPH oxidase,
    producing a nonworking protein. Of the following,
    which is most directly responsible for his susceptibility
    to infections?
    A. Elevated concentrations of reactive oxygen
    species
    B. Decreased concentrations of reactive oxygen
    species
    C. Elevated concentrations of activated
    α1-antitrypsin
    D. Decreased concentrations of activated
    α1-antitrypsin
    E. Elevated concentrations of C3a and C5a
    F. Decreased concentrations of C3a and C5a
A
  1. Correct: Decreased concentrations of
    reactive oxygen species (B)
    NADPH oxidase helps to synthesize reactive oxygen
    species, which then play a role in killing of infectious
    agents (A-B). α1-antitrypsin is an enzyme that
    is contained in fluids but is not activated directly by
    NADPH oxidase, and it plays a role in inhibiting the
    action of enzymes (C-D). C3a and C5a increase vascular
    permeability and induce vasodilation as well
    as play a role in recruitment of neutrophils, but they
    are produced by the action of neutral proteases and
    not NADPH oxidase (E-F).
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14
Q
  1. A 17-year-old female is brought to the emergency
    room by her family because she is acutely
    short of breath. Despite being given oxygen and epinephrine,
    her shortness of breath continues and she
    requires intubation. During the intubation, the emergency
    room physician notes severe laryngeal edema.
    This woman has a hereditary condition and commonly
    develops edema of soft tissue in various locations.
    Which of the following proteins does she lack?
    A. C5
    B. C3
    C. C3 inhibitor
    D. C1 inhibitor
    E. Decay-accelerating factor
A
  1. Correct: C1 inhibitor (D)
    The patient has hereditary angioedema, which is an
    inherited defect in C1 inhibitor (C), leading to edema
    of soft tissue, which can involve the larynx. (A-B,
    D-E) are incorrect.
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15
Q
  1. A pathologist is examining a slide of the
    appendix. In the mucosa, submucosa, and muscularis
    are numerous cells with abundant cytoplasm and
    multilobed nuclei, with the lobes joined by very thin
    bridges. Of the following mediators, which was most
    responsible for attracting these cells to this site?
    A. Leukotriene B4
    B. Leukotriene C4
    C. Leukotriene D4
    D. Leukotriene E4
    E. Substance P
A
  1. Correct: Leukotriene B4 (A)
    The cell type described is a neutrophil, which is
    an acute inflammatory cell. The disease that the
    patient has is acute appendicitis. Leukotriene B4 is
    a chemoattractant and plays a role in attracting neutrophils to the site of acute inflammation (A). The
    remainder of the mediators, including substance P,
    are primarily involved in increasing vascular permeability
    (B-E), so each of these mediators could play
    a role in the disease process of acute appendicitis;
    however, that role would not be as a chemoattractant.
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16
Q
  1. A pathologist is examining a slide and identifies
    a lesion that is a roughly circular collection of
    epithelioid macrophages. There is no central necrosis.
    Of the following organisms, which is the most
    likely cause of this lesion?
    A. Staphylococcus aureus
    B. Streptococcus pneumoniae
    C. Escherichia coli
    D. Pseudomonas aeruginosa
    E. Mycobacterium leprae
A
  1. Correct: Mycobacterium leprae (E)
    The lesion described is a granuloma. Granulomas are
    composed of epithelioid macrophages (also referred
    to as epithelioid histiocytes). While multinucleated
    giant cells are often found in granulomas, their presence
    is not necessary for the diagnosis of a granuloma.
    Granulomatous inflammation is produced by a
    variety of infectious agents as well as foreign material
    and other processes. Of the organisms listed, Mycobacterium leprae produces granulomatous inflammation (E), whereas the other organisms are not
    associated with granulomatous inflammation (A-D).
17
Q
  1. A 56-year-old alcoholic male is admitted to
    the hospital with a diagnosis of pneumonia. His primary
    care physician orders a test that identifies an
    increased speed of sedimentation of red blood cells.
    Which of the following mediators is responsible for
    this change?
    A. C-reactive protein
    B. Serum amyloid A
    C. Ceruloplasmin
    D. Fibrinogen
    E. Creatine kinase
A
  1. Correct: Fibrinogen (D)
    Fibrinogen is an acute phase protein; its concentration
    is elevated in acute inflammatory processes,
    such as pneumonia. Fibrinogen binds to red blood
    cells and thus causes rouleaux, which increases
    the sedimentation rate (C). The test ordered was
    the erythrocyte sedimentation rate. (A-B, D-E) are
    incorrect.
18
Q
  1. A 68-year-old male with metastatic lung cancer
    is being evaluated by his oncologist. His chemotherapy
    regimen was discontinued 3 months ago due to his
    poor prognosis. His wife is concerned because he has
    lost 25 lbs. over the past two months. At the present
    time he is on no medications, and she reports his appetite
    has been poor. Which of the following polypeptides
    released by immune cells in response to this patient’s
    cancer is most likely to cause progressive weight loss?
    A. TNF-α
    B. TGF-β
    C. IL-8
    D. IL-10
    E. IL-13
A
  1. Correct: TNF-α (A)
    TNF-α, IL-1, and IL-6 are proinflammatory cytokines
    that play a critical role in malignancy-related
    cachexia, and in experimental models, antagonists
    of these cytokines have been shown to mitigate this
    effect (A). TGF-β is an anti-inflammatory cytokine
    involved in cellular repair (B). IL-8 is a chemokine that
    recruits neutrophils to the site of infection or inflammation
    (C). IL-10 also plays a critical role in modulating
    the immune response by down-regulating the
    expression of Th1 cytokines, MHC class II antigens,
    and co-stimulatory molecules on macrophages and
    inhibiting the production of proinflammatory cytokines
    (D). In addition to its anti-inflammatory properties,
    IL-13 plays an important role in immunity to
    parasitic infections (E).
19
Q
  1. An immunologist studying the process of leukocyte
    recruitment in acute inflammation wishes to
    block the process of transmigration of neutrophils
    across the endothelial wall. A monoclonal antibody
    against which of the following adhesion molecules
    would inhibit transmigration (diapedesis) without
    interfering with rolling or margination?
    A. P-selectin
    B. E-selectin
    C. Integrin
    D. ICAM-1
    E. PECAM-1 (CD31)
A
  1. Correct: PECAM-1 (CD31) (E)
    PECAM-1 (E) plays a critical role in transmigration
    of the leukocyte across the vessel wall (E). The selectins
    form weak adhesions between leukocytes and
    endothelial cells, which slows the leukocytes during
    the process of rolling (A, B). Integrins (VLA-4, Mac-1,
    and LFA-1) on the leukocyte surface bind to ligands
    on the endothelial surface (ICAM-1, VCAM-1) after
    the initial process of leukocyte rolling (C, D). These
    interactions result in tight adherence of leukocytes
    to the vessel wall in preparation for diapedesis into
    the extravascular site of inflammation.
20
Q
  1. A 70-year-old male dies of an acute ischemic
    stroke. During the autopsy an incidental lesion is found
    in the apex of the right upper lobe of the lung. Microscopy
    reveals abundant macrophages with indistinct cell
    boundaries, surrounded by a rim of lymphocytes, and a
    central zone of necrotic debris. Of the following, which
    is the most likely cause of this patient’s lung lesion?
    A. Tissue foreign bodies
    B. Tuberculosis
    C. Sarcoidosis
    D. Crohn’s disease
    E. Leprosy
A
  1. Correct: Tuberculosis (B)
    The microscopic description is that of a granuloma
    with a central area of necrosis (i.e., caseous necrosis).
    Granulomatous inflammation with caseous
    necrosis is the classic finding in Mycobacterium
    tuberculosis infection (B). This central necrosis has a
    “cheesy” appearance on gross examination, hence the
    term “caseous.” All the other conditions mentioned
    are associated with granulomatous inflammation,
    though not usually with caseous necrosis (A, C-E).
    Crohn’s disease would not affect the lung (D), and
    leprosy involves the skin (E). Sarcoidosis is a granulomatous disease that most commonly involves the lung, although any other organ can also be involved.
    Granulomas in sarcoidosis are most commonly non-caseating; however, caseous necrosis has been found
    in patients with sarcoidosis. The fact that the lesion is
    in the apex of the lung also supports tuberculosis over
    sarcoidosis, as Mycobacterium tuberculosis is most
    commonly associated with the upper lobes of the lung
    because of the organism’s aerophilic nature.
21
Q
  1. A researcher is investigating an experimental
    drug (F-104), which is known to cause liver failure
    in mice. Which of the following microscopic findings
    would suggest that F-104 acted by inducing apoptosis
    rather than necrosis of the hepatic parenchymal cells?
    A. Cytoplasmic blebbing
    B. Hepatocyte swelling
    C. Chromatin condensation
    D. Abundant myelin figures
    E. Numerous inflammatory cells
A
  1. Correct: Chromatin condensation (C)
    Of the choices, chromatin condensation (C) is the
    most characteristic finding in apoptotic cells. Cytoplasmic
    blebbing could be seen in either apoptosis or necrosis (A). Cellular swelling, myelin figures, and abundant inflammatory cells are seen in necrosis,
    not apoptosis (B, D-E).
22
Q
  1. In the previous experiment, which of the following
    findings would support the hypothesis that
    F-104-induced apoptosis via the intrinsic pathway?
    A. Monoclonal antibody that blocks TNF receptor
    prevents F-104-induced liver injury
    B. Monoclonal antibody that blocks Fas prevents
    F-104-induced liver injury
    C. An experimental drug that inhibits cytochrome c
    release prevents F-104-induced liver injury
    D. An experimental drug that inhibits caspase 8
    prevents F-104-induced liver injury
    E. An experimental drug that inhibits caspase 10
    prevents F-104-induced liver injury
A
  1. Correct: An experimental drug that inhibits
    cytochrome c release prevents F-104-induced liver
    injury (C).
    Cytochrome c release from the mitochondria triggers
    apoptosis via the intrinsic (mitochondrial) pathway.
    Inhibiting this critical step in activation of the intrinsic
    pathway would be expected to interfere with
    F-104 if it acted via the intrinsic pathway (C). All the
    other effects, if observed, would support the hypothesis
    that F-104 induces apoptosis via the extrinsic
    (receptor-mediated) pathway (A-B, D-E).
23
Q
  1. A 56-year-old male presents to an acute care
    clinic with complaints of shortness of breath and fever.
    He has no past history of cigarette use. His vital signs
    are temperature of 101°F, pulse of 107 bpm, and blood
    pressure of 131/86 mm Hg. A chest X-ray reveals fluid
    in the left side of the chest and patchy consolidation
    of the lower lobe of the left lung. He is admitted to the
    hospital and a thoracentesis is performed. Of the following,
    what is most likely a characteristic of the fluid?
    A. Watery and clear
    B. Few cells identified on smear
    C. Low specific gravity
    D. Elevated protein
    E. Numerous neoplastic cells identified on smear
A
  1. Correct: Elevated protein (D)
    Given the clinical scenario (shortness of breath and
    fever associated with pulmonary consolidation),
    the patient most likely has bronchopneumonia, and
    the infiltrate in the pleural cavity is most likely an
    empyema, which is a form of exudate (D). Exudates
    are characteristically very cellular, have a high protein
    and lactate dehydrogenase concentration, and
    have a high specific gravity. Exudates can occur as a
    result of infection (e.g., an empyema) or lymphatic
    obstruction, such as due to a lymphoma. Transudates
    have low cellularity, low concentration of protein,
    and low specific gravity (A-C). A pleural effusion can
    be malignant, such as due to primary effusion lymphoma, bronchogenic carcinoma, or metastatic disease (E); however, this diagnosis would be much less
    likely without a contributing history, and the presentation
    is consistent with pneumonia.